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1

Apoptotic mechanisms in T47D and MCF7 human breast cancer cells  

Microsoft Academic Search

To investigate the mechanisms underlying apoptosis in breast cancer cells, staurosporine was used as an apoptotic stimulus in the human breast cancer cell lines MCF-7 and T47D. Staurosporine induced dose and time dependent increases in DNA fragmentation which was abrogated by z-VAD-fmk. MCF-7 cells did not express caspase-3, suggesting that DNA fragmentation occurred in the absence of caspase-3 and that

L M Mooney; K A Al-Sakkaf; B L Brown; P R M Dobson; PRM Dobson

2002-01-01

2

Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line  

Microsoft Academic Search

To evaluate whether leptin plays a putative role in breast tumorigenesis, we studied the expression of its long and short receptor isoforms in various tumoral breast tissues. We applied semiquantitative RT-PCR method to RNA extracted from 20 breast cancer biopsies and two human breast cancer cell lines (T47-D and MCF-7). Our results showed the expression of both leptin receptor transcripts

K. Laud; I. Gourdou; L. Pessemesse; J. P. Peyrat; J. Djiane

2002-01-01

3

Progestin Regulation of Alkaline Phosphatase in the Human Breast Cancer Cell Line T47D1  

Microsoft Academic Search

In T47D breast cancer cell line, progestin (R5020) induces de novo synthesis of an alkaline phosphatase enzyme. Based on inhibitor profiles and antigenic specificity, it is apparent that this enzyme belongs to the class of membrane-associated tissue-unspecific alkaline phosphatases. Enzyme induction was uniquely specific to progestins and not altered by other steroid hormones or synthetic analogues. The progestin induction of

Diego Di Lorenzo; Alberto Albertini; David Zava

1991-01-01

4

Estradiol increases the production of alpha 1-antichymotrypsin in MCF7 and T47D human breast cancer cell lines.  

PubMed

alpha 1-Antichymotrypsin (Achy) is an antiprotease of the acute inflammation phase, which is also released by MCF7 human breast cancer cells in culture. Using a fluorimetric assay with the synthetic substrate L-Seryl-L-Tyrosyl-2-N-naphthylamide, we have shown that a medium conditioned by MCF7 cells treated by estradiol inhibits the activity of alpha-chymotrypsin. This inhibition increased when physiological concentrations of estradiol were added to the cells for 2 days. It was due to an increased production of Achy and not to a direct effect of estradiol on alpha-chymotrypsin activity as shown by double immunoprecipitation with an antiserum against human alpha 1-antichymotrypsin. An increased accumulation by estradiol of an antigen located in the cytoplasm of MCF7 cells, which was revealed by immunoperoxidase staining with antibodies to Achy, also indicated that estradiol increased the production of Achy in these cells. Similar immunostaining was observed in a breast cancer tissue. Most of the estrogen regulated 60-68 kDa protein secreted by T47D cells (Chalbos et al. (1982) J. Clin. Endocrinol. Metab. 55, 276-283) was also specifically immunoprecipitated by the antibodies to Achy. Thus, alpha 1-antichymotrypsin is the first protein to be identified which is induced by estradiol and secreted by breast cancer cells. PMID:3899774

Massot, O; Baskevitch, P P; Capony, F; Garcia, M; Rochefort, H

1985-10-01

5

SR140333 counteracts NK-1 mediated cell proliferation in human breast cancer cell line T47D  

PubMed Central

Background It has been demonstrated that certain NK-1 antagonists could reduce proliferation of several cancer cell lines, however, it is unknown whether SR140333 exerts proliferation inhibition in breast cancer cell line. Methods Immunohistochemical staining was carried out to investigate the immunolocation of NK-1 in breast cancer tissues and T47D cell line, thereafter, various concentrations of [Sar9, Met(O2)11]substance P and SR140333 were applied alone or combined. MTT assay was applied to detect cytoactivation and coulter counter was to detect growth curve. The Hoechst33258 staining was performed to detect apoptosis. Results We found that breast cancer and T47D cells bear positive expression of NK-1. SR140333 inhibited cell growth in a dose dependent manner. Furthermore, SR140333 could counteract [Sar9, Met(O2)11]substance P induced proliferation. Hoechst33258 staining revealed the presence of apoptosis after SR140333 treatment. Conclusions Our study demonstrated SR140333 exert proliferation inhibition in breast cancer cell line T47D and indicates NK-1 play a central role in the substance P related cell proliferation in breast cancer.

2010-01-01

6

In vivo phosphorylation of progesterone receptors in the T47D sub co human breast cancer cell line  

SciTech Connect

We have had evidence indicating that human progesterone receptors (PR) are phosphoproteins, and used metabolic labeling with ({sup 35}S)methionine and ({sup 32}P)orthophosphate to study the synthesis, structure, and phosphorylation of PR in T47D{sub co} human breast cancer cells, a cell line extremely rich for PR. Human PR exist as two independent hormone-binding proteins; B-receptors which are triplets in SDS-gels (M{sub r} 114, 117, and 120 kDa), and A-receptors that are a single band (94 kDa). The work presented here documents that human A- and B-receptors are phosphorylated on serine residues in the untransformed state, with phosphate being incorporated into all three bands of the B-proteins. However, a brief ({sup 35}S)methionine pulse shows that both A and B are synthesized as singlets of 94 and 114 kDa, respectively. The B-triplet is formed post-translationally by slow phosphorylation. B-triplet formation, or maturation, can be reversed by treatment with calf alkaline phosphatase or stabilized by the presence of phosphatase inhibitors. Additional ({sup 35}S)labeling studies in the presence of progestins demonstrate that receptors that are 15 min old are able to bind hormone and transform to the tight nuclear binding state.

Sheridan, P.L.

1989-01-01

7

31P-NMR studies of phosphate transfer rates in T47D human breast cancer cells.  

PubMed

The concentration of phosphates and the kinetics of phosphate transfer reactions were measured in the human breast cancer cell line, T47D, using 31P-NMR spectroscopy. The cells were embedded in agarose filaments and perifused with oxygenated medium during the NMR measurements. The following phosphates were identified in spectra of perifused cells and of cell extracts: phosphorylcholine (PC), phosphorylethanolamine (PE), the glycerol derivatives of PC and PE, inorganic phosphate (Pi), phosphocreatine (PCr), nucleoside triphosphate (primarily ATP) and uridine diphosphate glucose. The rates of the transfers: PC----gamma ATP (0.2 mM/s), Pi----gamma ATP (0.2 mM/s) and the conversion beta ATP----beta ADP (1.3 mM/s) were determined from analysis of data obtained in steady-state saturation transfer and inversion recovery experiments. Data from spectrophotometric assays of the specific activity of creatine kinase (approx. 0.1 mumol/min per mg protein) and adenylate kinase (approx. 0.4 mumol/min per mg protein) suggest that the beta ATP----beta ADP rate is dominated by the latter reaction. The ratio between the rate of ATP synthesis from Pi and the rate of consumption of oxygen atoms (4 X 10(-3) mM/s) was approx. 50. This high value and preliminary measurements of the rate of lactate production from glucose, indicated that aerobic glycolysis is the main pathway of ATP synthesis. PMID:3620515

Neeman, M; Rushkin, E; Kaye, A M; Degani, H

1987-09-14

8

Differential regulation of the human 'leukemia inhibitory factor' (LIF) promoter in T47D and MDA-MB 231 breast cancer cells  

Microsoft Academic Search

Leukemia inhibitory factor (LIF) is a pleiotropic inflammatory cytokine. A potential role for LIF in the pathogenesis of human breast cancer was recently indicated by the finding that LIF is produced by MDA-MB 231 breast cancer cells and that it stimulates proliferation of the T47D and MCF-7 breast cancer cell lines. Despite its role as a possible therapeutic target in

Ana-Maria Bamberger; Imke Thuneke; Heinrich M. Schulte

1998-01-01

9

Upregulation of cytokeratins 8 and 18 in human breast cancer T47D cells is retinoid-specific and retinoic acid receptor-dependent  

Microsoft Academic Search

The mamary gland is chiefly composed of luminal epithelial cells expressing cytokeratins (K) 8, 18 and 19, and basal\\/myoepithelial cells expressing cytokeratins 5 and 14. Human breast cancer T47D cells have a luminal phenotype and are growth-inhibited by retinoids, a class of compounds known to regulate cytokeratin expression. To extend our knowledge of retinoid action in breast cancer, we have

Yongkui Jing; Jie Zhang; Samuel Waxman; Rafael Mira-y-Lopez

1996-01-01

10

Differential Responsiveness of Human Breast Cancer Cell Lines MCF7 and T47D to Growth Factors and 170Estradiol1  

Microsoft Academic Search

A completely serum-free assay method has been used to compare the mitogenic activities of polypeptide growth factors and estrogens with MCF-7 and T47D human breast cancer cells in culture. The lines were maintained in a viable, slowly dividing condition in Ham's F12 and Dulbecco's modified Eagle's medium (1:1) supplemented with sodium bicarbonate (2.2 g\\/liter), 15 HIM4-(2-hydroxyethyl)-l-piperazineethane- sulfonic acid, human transferrin

Kenneth P. Karey; David A. Sirbasku

11

Resveratrol-Induced Apoptosis Is Associated with Activation of p53 and Inhibition of Protein Translation in T47D Human Breast Cancer Cells  

Microsoft Academic Search

Background and Purpose:Trans-resveratrol (RSVL; 3,4?,5-trihydroxystilbene), a natural compound found in grapes, berries, peanuts and red wine exerts certain anticancer roles in different human cancer types. However, the exact molecular mechanism(s) behind such a role remains to be elucidated, thus the aim of this study. Experimental Approach: T47D human breast cancer cells were treated with RSVL and cell proliferation was measured

Moussa Alkhalaf

2007-01-01

12

Comparative cellular and molecular analysis of cytotoxicity and apoptosis induction by doxorubicin and Baneh in human breast cancer T47D cells  

Microsoft Academic Search

It is now widely accepted that dietary phytochemicals inhibit cancer progression and enhance the effects of conventional chemotherapy.\\u000a In this report, we comparatively studied the cellular and molecular aspects of apoptosis induction by the methanolic extract\\u000a of Baneh fruit skin in comparison to Doxorubicin (Dox), a well-known anticancer drug, in human breast cancer T47D cells. The MTT assay was used

P. Fathi Rezaei; Sh. Fouladdel; Silvia Cristofanon; S. M. Ghaffari; G. R. Amin; E. Azizi

13

Indole3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells  

Microsoft Academic Search

Indole-3-carbinol (I3C) is a major component of Brassica vegetables, and diindolylmethane (DIM) is the major acid-catalyzed condensation product derived from I3C. Both compounds competitively bind to the aryl hydrocarbon (Ah) receptor with relatively low affinity. In Ah-responsive T47D human breast cancer cells, I3C and DIM did not induce significantly CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity or CYP1A1 mRNA levels at concentrations

Ichen Chen; Stephen Safe; Leonard Bjeldanes

1996-01-01

14

Estradiol stimulates expression of two human prolactin receptor isoforms with alternative exons-1 in T47D breast cancer cells  

Microsoft Academic Search

Human prolactin receptor (hPRLR) expression is regulated by estradiol-17? (E2) in vivo in animal tissues, and in vitro in normal human endometrial cells and in MCF7 human breast cancer cells. The objective of this study was to determine the effect of E2 on the expression of two recently described hPRLR isoforms with distinct exons-1, hE13 and hE1N1 that are transcribed

Mark P Leondires; Zhang-Zhi Hu; Juying Dong; Chon-Hwa Tsai-Morris; Maria L Dufau

2002-01-01

15

Identification and characterization of microRNAs expressed in human breast cancer T-47D cells in response to prolactin treatment by Solexa deep-sequencing technology.  

PubMed

MicroRNAs (miRNAs) are key regulators of gene expression and perform critical roles in various biological processes. To investigate the functional roles of miRNAs in the prolactin receptor (PRLR) signaling pathway in breast cancer, we constructed two small RNA libraries from human breast cancer T-47D cells treated with or without prolactin (PRL). The miRNA expression profiles were systematically screened using Solexa deep-sequencing technology. More than 40 miRNAs were significantly differentially expressed, from which 4 miRNAs were chosen for validation by stem-loop real-time PCR. In addition, 3 novel miRNAs were selected for verification by PCR. Furthermore, upstream miRNA target genes were predicted using different algorithms, GO and KEGG analyses revealed that these targets were highly related to the PRLR signaling pathway. This study provides a reference for elucidating the complex miRNA-mediated regulatory networks of PRL/PRLR signaling pathway that affect breast cancer tumorigenesis and progression. PMID:23410749

Wei, Qinjun; He, Wei; Yao, Jun; Guo, Li; Lu, Yajie; Cao, Xin

2013-02-11

16

Identification and Androgen Regulation of Two Proteins Released by T47D Human Breast Cancer Cells1  

Microsoft Academic Search

Three (35S|methionine-labeledpolypeptides released by T47Dhuman breast cancer cells have been identified as corresponding to two proteins previously described in breast gross cystic disease fluid. A M, 43,000 protein was immunoprecipitated by polyclonal antibodies to the 7,n-«2- glycoprotein. A M, 18,000 and a M, 13,000 polypeptide were both immunoprecipitated by four monoclonal antibodies directed against four separate epitopes of M, 15,000

D. Chalbos; D. Haagensen; T. Parish; H. Rochefort

17

Apoptotic effects of Physalis minima L. chloroform extract in human breast carcinoma T-47D cells mediated by c-myc-, p53-, and caspase-3-dependent pathways.  

PubMed

The chloroform extract of Physalis minima produced a significant growth inhibition against human T-47D breast carcinoma cells as compared with other extracts with an EC(50) value of 3.8 microg/mL. An analysis of cell death mechanisms indicated that the extract elicited an apoptotic cell death. mRNA expression analysis revealed the coregulation of apoptotic genes, that is, c-myc , p53, and caspase-3. The c-myc was significantly induced by the chloroform extract at the earlier phase of treatment, followed by p53 and caspase-3. Biochemical assay and ultrastructural observation displayed typical apoptotic features in the treated cells, including DNA fragmentation, blebbing and convolution of cell membrane, clumping and margination of chromatin, and production of membrane-bound apoptotic bodies. The presence of different stages of apoptotic cell death and phosphatidylserine externalization were further reconfirmed by annexin V and propidium iodide staining. Thus, the results from this study strongly suggest that the chloroform extract of P. minima induced apoptotic cell death via p53-, caspase-3-, and c-myc-dependent pathways. PMID:20150224

Ooi, Kheng Leong; Tengku Muhammad, Tengku Sifzizul; Lim, Chui Hun; Sulaiman, Shaida Fariza

2010-02-11

18

Lipid metabolism in T47D human breast cancer cells: 31P and 13C-NMR studies of choline and ethanolamine uptake.  

PubMed

31P and 13C-NMR were used to determine the kinetics of choline and ethanolamine incorporation in T47D clone 11 human breast cancer cells grown as small (150 microns) spheroids. Spheroids were perfused inside the spectrometer with 1,2-13C-labeled choline or 1,2-13C-labeled ethanolamine (0.028 mM) and the buildup of labeled phosphoryl-choline (PC) or phosphorylethanolamine (PE) was monitored. Alternatively the PC and GPC pools were prelabeled with 13C and the reduction of label was monitored. 31P spectra were recorded from which the overall energetic status as well as total pool sizes could be determined. The ATP content was 8 +/- 1 fmol/cell, and the total PC and PE pool sizes were 16 and 14 fmol/cell, respectively. PC either increased by 50% over 24 h or remained constant, while PE remained constant in medium without added ethanolamine but increased 2-fold within 30 h in medium containing ethanolamine, indicating a dependence on precursor concentration in the medium. The 31P and 13C data yielded similar kinetic results: the rate of the enzymes phosphocholine kinase and phosphoethanolamine kinase were both on the order of 1.0 fmol/cell per h, and the rate constants for CTP:phosphocholine cytidyltransferase and CTP:phosphoethanolamine kinase were 0.06 h-1 for both enzymes. The kinetics of choline incorporation did not alter in the presence of 0.028 mM ethanolamine indicating that they have non-competing pathways. PMID:1657190

Ronen, S M; Rushkin, E; Degani, H

1991-10-16

19

Lipid metabolism in large T47D human breast cancer spheroids: 31P- and 13C-NMR studies of choline and ethanolamine uptake.  

PubMed

31P- and 13C-NMR were used to determine the kinetics of choline and ethanolamine incorporation in T47D clone 11 human breast cancer cells grown as large (300 microns) spheroids. Spheroids were perfused inside the spectrometer with 1,2-13C-labeled choline or ethanolamine (0.028 mM) and the buildup of labeled phosphorylcholine (PC) or phosphorylethanolamine (PE) was monitored. To analyze the NMR kinetic data, it was assumed that each signal represents a weighted average of signal from the proliferating and non-proliferating compartments of the large spheroid. The average ATP pool size was 4 +/- 1 fmol/cell compared to 8 +/- 1 fmol/cell in small (150 microns) proliferating spheroids (P less than 0.0002). The average PC pool size at steady state was reduced to 11 +/- 6 fmol/cell compared to 22 +/- 8 (P less than 0.007). This could be correlated with an overall reduction of choline uptake in the non-proliferating spheroid fraction. The rate of the enzyme choline kinase was 0.3 fmol/(cell h) compared to 1.0 fmol/(cell h) (P less than 0.0001) for proliferating cells. The rate constant of CTP:phosphocholine cytidyltransferase (0.05 h-1) was not significantly altered, but the rate of the enzyme was reduced from 1.3 to 0.2-0.5 fmol/(cell h). The pool size of PE in medium containing serum ethanolamine (1.7 microM) was approximately the same (15 fmol/cell) in small and large spheroids. In the presence of high ethanolamine (0.028 mM) the average PE level decreased slightly (11 fmol/cell) and the rate of the enzyme ethanolamine kinase in the non-proliferating fraction was 0.7 fmol/(cell h) versus 1.0 fmol/(cell h) in the proliferating cells (P less than 0.07). The rate constant of CTP:phosphoethanolamine cytidyltransferase (0.07 h-1) was not significantly altered but the corresponding reaction rate was reduced from 1.4 to 0.2-0.8 fmol/(cell h). The kinetics of choline incorporation did not alter in the presence of 0.028 mM ethanolamine. PMID:1547282

Ronen, S M; Rushkin, E; Degani, H

1992-03-20

20

Revealing the Anti-Tumor Effect of Artificial miRNA p-27-5p on Human Breast Carcinoma Cell Line T-47D  

PubMed Central

microRNAs (miRNAs) cause mRNA degradation or translation suppression of their target genes. Previous studies have found direct involvement of miRNAs in cancer initiation and progression. Artificial miRNAs, designed to target single or multiple genes of interest, provide a new therapeutic strategy for cancer. This study investigates the anti-tumor effect of a novel artificial miRNA, miR P-27-5p, on breast cancer. In this study, we reveal that miR P-27-5p downregulates the differential gene expressions associated with the protein modification process and regulation of cell cycle in T-47D cells. Introduction of this novel artificial miRNA, miR P-27-5p, into breast cell lines inhibits cell proliferation and induces the first “gap” phase (G1) cell cycle arrest in cancer cell lines but does not affect normal breast cells. We further show that miR P-27-5p targets the 3?-untranslated mRNA region (3?-UTR) of cyclin-dependent kinase 4 (CDK4) and reduces both the mRNA and protein level of CDK4, which in turn, interferes with phosphorylation of the retinoblastoma protein (RB1). Overall, our data suggest that the effects of miR p-27-5p on cell proliferation and G1 cell cycle arrest are through the downregulation of CDK4 and the suppression of RB1 phosphorylation. This study opens avenues for future therapies targeting breast cancer.

Tseng, Chien-Wei; Huang, Hsuan-Cheng; Shih, Arthur Chun-Chieh; Chang, Ya-Ya; Hsu, Chung-Cheng; Chang, Jen-Yun; Li, Wen-Hsiung; Juan, Hsueh-Fen

2012-01-01

21

Induction of G1 cell cycle arrest and cyclin D1 down-regulation in response to pericarp extract of Baneh in human breast cancer T47D cells  

PubMed Central

Background and the purpose of the study Natural products from plants have an important role in the development and production of new drugs mainly for cancer therapy. More recently, we have shown that the pericarp methanolic extract of Pistacia atlantica sub kurdica (with local name of Baneh) as a rich source of active biological components with high antioxidant and radical scavenging activities, has ability to cease proliferation and induce apoptosis in T47D human breast cancer cells. The present study aimed to clarify whether Baneh extract able to alter cell cycle progression of T47D cells or not. Methods In order to study the possible effect of Baneh extract on cell cycle of T47D cells, we evaluated cell cycle distribution and its regulatory proteins by flow cytometry and western blot analysis respectively. Results Baneh extract induced G0/G1 cell cycle arrest in conjunction with a marked decrease in expression of cyclin D1 and cdk4 that was strongly dependent on time of exposure. In parallel, Dox-treated T47D cells in early time points were accumulated on S phase, but after 48 h cell cycle progression was inhibited on G2/M. Dox promoted striking accumulation of cyclin B1 rapidly and enhanced cyclin A abundance. Conclusion Taken together, our results establish that the antitumor activity of the pericarp extract of Baneh partly is mediated via cell cycle arrest and downregulation of cyclin D1 and cdk4 expression. These findings warrant further evaluation regarding the mechanism(s) of action of this promising anticancer agent.

2012-01-01

22

Cytotoxic response of breast cancer cell lines, MCF 7 and T 47 D to triphala and its modification by antioxidants  

Microsoft Academic Search

The cytotoxic effects of Triphala (TPL), an Indian Ayurvedic formulation with known anti-cancer properties, has been investigated on two human breast cancer cell lines differing in their p53 status. In vitro studies showed that MCF 7 with wild type p53 was more sensitive to TPL than T 47 D, which is p53 negative. TPL induced loss of cell viability was

T. Sandhya; K. P. Mishra

2006-01-01

23

Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: Roles of PAH interactions and PAH metabolites  

SciTech Connect

The interactions of polycyclic aromatic hydrocarbons (PAH) and cytochromes P450 (CYP) are complex; PAHs are enzyme inducers, substrates, and inhibitors. In T-47D breast cancer cells, exposure to 0.1 to 1 {mu}M benzo(k)fluoranthene (BKF) induced CYP1A1/1B1-catalyzed 17{beta}-estradiol (E{sub 2}) metabolism, whereas BKF levels greater than 1 {mu}M inhibited E{sub 2} metabolism. Time course studies showed that induction of CYP1-catalyzed E{sub 2} metabolism persisted after the disappearance of BKF or co-exposed benzo(a)pyrene, suggesting that BKF metabolites retaining Ah receptor agonist activity were responsible for prolonged CYP1 induction. BKF metabolites were shown, through the use of ethoxyresorufin O-deethylase and CYP1A1-promoter-luciferase reporter assays to induce CYP1A1/1B1 in T-47D cells. Metabolites formed by oxidation at the C-2/C-3 region of BKF had potencies for CYP1 induction exceeding those of BKF, whereas C-8/C-9 oxidative metabolites were somewhat less potent than BKF. The activities of expressed human CYP1A1 and 1B1 with BKF as substrate were investigated by use of HPLC with fluorescence detection, and by GC/MS. The results showed that both enzymes efficiently catalyzed the formation of 3-, 8-, and 9-OHBKF from BKF. These studies indicate that the inductive effects of PAH metabolites as potent CYP1 inducers are likely to be additional important factors in PAH-CYP interactions that affect metabolism and bioactivation of other PAHs, ultimately modulating PAH toxicity and carcinogenicity.

Spink, David C. [Wadsworth Center, New York State Department of Health, Albany, NY 12201-0509 (United States)], E-mail: spink@wadsworth.org; Wu, Susan J.; Spink, Barbara C.; Hussain, Mirza M.; Vakharia, Dilip D.; Pentecost, Brian T.; Kaminsky, Laurence S. [Wadsworth Center, New York State Department of Health, Albany, NY 12201-0509 (United States)

2008-02-01

24

Influence of Cellular ER \\/ER  Ratio on the ER Agonist Induced Proliferation of Human T47D Breast Cancer Cells  

Microsoft Academic Search

Breast cancer cells show overexpression of estrogen receptor (ER) a relative to ERb compared to normal breast tissues. This observation has lead to the hypothesis that ERb may modulate the proliferative effect of ERa. This study investigated how variable cellular expression ratios of the ERa and ERb modulate the effects on cell proliferation induced by ERa or ERb agonists, respectively.

Ana Maria Sotoca Covaleda; Hans van den Berg; Jacques Vervoort; Paul van der Saag; Anders Strom; J.-A. Gustafsson; I. Rietjens; A. J. Murk

2008-01-01

25

Biotin uptake by T47D breast cancer cells: functional and molecular evidence of sodium-dependent multivitamin transporter (SMVT).  

PubMed

The objective of this study was to investigate functional and molecular evidence of carrier mediated system responsible for biotin uptake in breast cancer (T47D) cells and to delineate mechanism of intracellular regulation of this transporter. Cellular accumulation of [3H] biotin was studied in T47D and normal mammary epithelial (MCF-12A) cells. Reverse transcription polymerase chain reaction (RT-PCR) was carried out to confirm the molecular expression of sodium dependent multivitamin transporter (SMVT) in T47D cells. Quantitative real time PCR analysis was also performed to compare the relative expression of SMVT in T47D and MCF-12A cells. [3H] biotin uptake by T47D cells was found to be concentration dependent with K(m) of 9.24 ?M and V(max) of 27.34 pmol/mg protein/min. Uptake of [3H] biotin on MCF-12A cells was also found to be concentration dependent and saturable, but with a relatively higher K(m) (53.10 ?M) indicating a decrease in affinity of biotin uptake in normal breast cells compared to breast cancer cells. [3H] biotin uptake appears to be time-, temperature-, pH- and sodium ion-dependent but independent of energy and chloride ions. [3H] biotin uptake was significantly inhibited in the presence of biotin, its structural analog desthiobiotin, pantothenic acid and lipoic acid. Concentration dependent inhibition of biotin uptake was evident in the presence of valeric acid which possesses free carboxyl group and biocytin and NHS biotin which are devoid of free carboxyl group. No significant inhibition was observed in the presence of structurally unrelated vitamins (ascorbic acid, folic acid, nicotinic acid, thiamine, pyridoxine and riboflavin). Modulators of PTK, PKC and PKA mediated pathways had no effect, but uptake in presence of calmidazolium (calcium-calmodulin inhibitor) was significantly inhibited. [3H] biotin uptake in the presence of calmidazolium was found to be saturable with a K(m) and V(max) values of 13.49 ?M and 11.20 pmol/mg protein/min, respectively. A band of SMVT mRNA at 774 bp was identified by RT-PCR analysis. Quantitative real time PCR confirmed higher expression of SMVT in T47D cells relative to MCF-12A cells. All these studies demonstrated for the first time the functional and molecular expression of sodium dependent multivitamin transporter (SMVT), a specific carrier-mediated system for biotin uptake, in human derived breast cancer (T47D) cells. The present study also indicated that cancer cells could import more vitamin compared to normal breast cells possibly for maintaining high proliferative status. We investigated the likelihood of selecting this cell line (T47D) as an in vitro cell culture model to study biotin-conjugated anti-cancer drugs/drug delivery systems. PMID:23142496

Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

2012-11-08

26

Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)  

Microsoft Academic Search

The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from (14C)acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed

Sheila M. Judge; Robert T. Chatterton

1983-01-01

27

Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)  

SciTech Connect

The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from (14C)acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed in larger numbers without concomitant accumulation of casein granules in cells incubated with progesterone, but secretion of lipid into the medium did not occur. An effect of progesterone on TG accumulation was detectable after 12 hr and was maximal at 72 hr. Increasing doses of progesterone (10(-9) to 10(-5) M) caused a progressive increase in TG accumulation. The presence of cortisol and/or prolactin did not alter TG formation nor the dose response of the cells to progesterone. The growth rate of T-47D cells was not altered by the presence of progesterone in the medium. Neither of the human mammary cancer cell lines, MCF-7 and HBL-100, nor the human fibroblast cell lines, 28 and 857, responded to progesterone. The data indicate that, while the normally lactogenic hormones do not stimulate milk product biosynthesis in the cell lines tested, progesterone specifically stimulated synthesis and accumulation of TG in the T-47D cells.

Judge, S.M.; Chatterton, R.T. Jr.

1983-09-01

28

Quantitative Proteomics and Transcriptomics Addressing the Estrogen Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed to the Phytoestrogen Genistein*  

PubMed Central

The present study addresses, by transcriptomics and quantitative stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics, the estrogen receptor ? (ER?) and ? (ER?)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line with tetracycline-dependent ER? expression (T47D-ER?), the effect of a varying intracellular ER?/ER? ratio on genistein-induced gene and protein expression was characterized. Results obtained reveal that in ER?-expressing T47D-ER? cells with inhibited ER? expression genistein induces transcriptomics and proteomics signatures pointing at rapid cell growth and migration by dynamic activation of cytoskeleton remodeling. The data reveal an interplay between integrins, focal adhesion kinase, CDC42, and actin cytoskeleton signaling cascades, occurring upon genistein treatment, in the T47D-ER? breast cancer cells with low levels of ER? and no expression of ER?. In addition, data from our study indicate that ER?-mediated gene and protein expression counteracts ER?-mediated effects because in T47D-ER? cells expressing ER? and exposed to genistein transcriptomics and proteomics signatures pointing at a clear down-regulation of cell growth and induction of cell cycle arrest and apoptosis were demonstrated. These results suggest that ER? decreases cell motility and metastatic potential as well as cell survival of the breast cancer cell line. It is concluded that the effects of genistein on proteomics and transcriptomics end points in the T47D-ER? cell model are comparable with those reported previously for estradiol with the ultimate estrogenic effect being dependent on the relative affinity for both receptors and on the receptor phenotype (ER?/ER? ratio) in the cells or tissue of interest.

Sotoca, Ana M.; Sollewijn Gelpke, Maarten D.; Boeren, Sjef; Strom, Anders; Gustafsson, Jan-?ke; Murk, Albertinka J.; Rietjens, Ivonne M. C. M.; Vervoort, Jacques

2011-01-01

29

Induction of CYP1A1 and CYP1B1 by benzo( k)fluoranthene and benzo( a)pyrene in T-47D human breast cancer cells: Roles of PAH interactions and PAH metabolites  

Microsoft Academic Search

The interactions of polycyclic aromatic hydrocarbons (PAH) and cytochromes P450 (CYP) are complex; PAHs are enzyme inducers, substrates, and inhibitors. In T-47D breast cancer cells, exposure to 0.1 to 1 ?M benzo(k)fluoranthene (BKF) induced CYP1A1\\/1B1-catalyzed 17?-estradiol (E2) metabolism, whereas BKF levels greater than 1 ?M inhibited E2 metabolism. Time course studies showed that induction of CYP1-catalyzed E2 metabolism persisted after the disappearance

David C. Spink; Susan J. Wu; Barbara C. Spink; Mirza M. Hussain; Dilip D. Vakharia; Brian T. Pentecost; Laurence S. Kaminsky

2008-01-01

30

Growth arrest of the breast cancer cell line, T47D, by TNF alpha; cell cycle specificity and signal transduction.  

PubMed Central

The effects of tumour necrosis factor-alpha (TNF alpha) on the growth and DNA synthesis of the human breast cell line, T47D, were studied. A dose-dependent, reversible inhibition of thymidine incorporation and cell growth was observed in the range of 0.1 ng ml-1 to 100 ng ml-1 of TNF alpha. Cell viability was not impaired in any of the experiments. Flow-cytometric DNA analysis demonstrated that after 24 h exposure to TNF alpha, T47D cells accumulated in the G1 phase of the cell cycle, and were depleted in the G2/M and S phases, suggesting a block in the progression of the G1/S transition. The involvement of protein kinases (PK) and protein phosphatases in TNF alpha-induced signal transduction was also investigated. A transient and rapid 2-fold increase in total cellular protein kinase C (PKC) activity was detected after 10 min exposure to TNF alpha. To study the role of the observed PKC activation in the cytostatic effect of TNF alpha, T47D cells were exposed to the cytokine in the presence of the potent PKC inhibitor, H7. The inhibitory effect of TNF alpha on thymidine incorporation was not affected by exposure to H7 at concentrations sufficient to block the stimulation of thymidine up-take induced by the PKC agonist, phorbol-12-myristate-13-acetate (PMA). The involvement of other signalling pathways was addressed using the cyclic nucleotide-dependent PK inhibitor, H8; the calmodulin-dependent PK inhibitor, W7; and the inhibitor of protein phosphatases PP1 and PP2B, okadaic acid. Exposure of T47D cells to these enzyme inhibitors failed to antagonise the inhibition of thymidine incorporation by TNF alpha. Taken together, these results indicate that the cytostatic effect of TNF alpha on T47D cells occurs at the G1/S transition of the cell cycle, and is mediated by an intracellular pathway which does not involve the activity of protein kinases C and A, nor protein phosphatases PP1, PP2B.

Pusztai, L.; Lewis, C. E.; McGee, J. O.

1993-01-01

31

Secretion of breast gross cystic disease fluid proteins by T47D breast cancer cells in culture — modulation by steroid hormones  

Microsoft Academic Search

Summary The effect of steroid hormones on modulating the secretion rates of three human breast gross cystic disease fluid proteins (GCDFP-15, GCDFP-24, and GCDFP-44) by T47D breast carcinoma cells in tissue culture was evaluated. Androgens (dihydrotestosterone or fluoxymesterone) were capable of stimulating the secretion rates for all three GCDFP's while showing a minimal trend toward slowing the growth rate of

Darrow E. Haagensen; Peter Stewart; William G. Dilley; Samuel A. Wells

1992-01-01

32

Cytotoxic Activities of Silver Nanoparticles and Silver Ions in Parent and Tamoxifen-Resistant T47D Human Breast Cancer Cells and Their Combination Effects with Tamoxifen against Resistant Cells  

PubMed Central

Studies on biomedical applications of nanoparticles are growing with a rapid pace. In medicine, nanoparticles may be the solution for multi-drug-resistance which is still a major drawback in chemotherapy of cancer. In the present study, we investigated the potential cytotoxic effect of silver nanoparticles (Ag NPs) and silver ions (Ag+) in both parent and tamoxifen-resistant T47D cells in presence and absence of tamoxifen. Ag NPs were synthesized (< 28 nm) and MTT assay was carried out. The associated IC50 values were found to be: 6.31 µg/ml for Ag NPs/parent cells, 37.06 µg/ml for Ag NPs/tamoxifen-resistant cells, 33.06 µg/ml for Ag+/parent cells and 10.10 µg/ml for Ag+/resistant cells. As a separate experiment, the effect of subinhibitory concentrations of Ag NPs and Ag+ on the proliferation of tamoxifen-resistant cells was evaluated at non-toxic concentrations of tamoxifen. Our results suggested that in non-cytotoxic concentrations of silver nanomaterials and tamoxifen, the combinations of Ag+-tamoxifen and Ag NPs-tamoxifen are still cytotoxic. This finding may be of great potential benefit in chemotherapy of breast cancer; since much lower doses of tamoxifen may be needed to produce the same cytotoxic effect and side effects will be reduced.

Ostad, Seyed Naser; Dehnad, Shahrzad; Nazari, Zeinab Esmail; Fini, Shohreh Tavajohi; Mokhtari, Narges; Shakibaie, Mojtaba; Shahverdi, Ahmad Reza

2010-01-01

33

Extranuclear ER? is associated with regression of T47D PKC?-overexpressing, tamoxifen-resistant breast cancer  

PubMed Central

Background Prior to the introduction of tamoxifen, high dose estradiol was used to treat breast cancer patients with similar efficacy as tamoxifen, albeit with some undesirable side effects. There is renewed interest to utilize estradiol to treat endocrine resistant breast cancers, especially since findings from several preclinical models and clinical trials indicate that estradiol may be a rational second-line therapy in patients exhibiting resistance to tamoxifen and/or aromatase inhibitors. We and others reported that breast cancer patients bearing protein kinase C alpha (PKC?)- expressing tumors exhibit endocrine resistance and tumor aggressiveness. Our T47D:A18/PKC? preclinical model is tamoxifen-resistant, hormone-independent, yet is inhibited by 17?-estradiol (E2) in vivo. We previously reported that E2-induced T47D:A18/PKC? tumor regression requires extranuclear ER? and interaction with the extracellular matrix. Methods T47D:A18/PKC? cells were grown in vitro using two-dimensional (2D) cell culture, three-dimensional (3D) Matrigel and in vivo by establishing xenografts in athymic mice. Immunofluoresence confocal microscopy and co-localization were applied to determine estrogen receptor alpha (ER?) subcellular localization. Co-immunoprecipitation and western blot were used to examine interaction of ER? with caveolin-1. Results We report that although T47D:A18/PKC? cells are cross-resistant to raloxifene in cell culture and in Matrigel, raloxifene induces regression of tamoxifen-resistant tumors. ER? rapidly translocates to extranuclear sites during T47D:A18/PKC? tumor regression in response to both raloxifene and E2, whereas ER? is primarily localized in the nucleus in proliferating tumors. E2 treatment induced complete tumor regression whereas cessation of raloxifene treatment resulted in tumor regrowth accompanied by re-localization of ER? to the nucleus. T47D:A18/neo tumors that do not overexpress PKC? maintain ER? in the nucleus during tamoxifen-mediated regression. An association between ER? and caveolin-1 increases in tumors regressing in response to E2. Conclusions Extranuclear ER? plays a role in the regression of PKC?-overexpressing tamoxifen-resistant tumors. These studies underline the unique role of extranuclear ER? in E2- and raloxifene-induced tumor regression that may have implications for treatment of endocrine-resistant PKC?-expressing tumors encountered in the clinic.

2013-01-01

34

Combination of low-concentration of novel phytoestrogen (8,9)-furanyl-pterocarpan-3-ol from Pachyrhizus erosus attenuated tamoxifen-associated growth inhibition on breast cancer T47D cells  

PubMed Central

Objective To investigate the estrogenic effect of (8,9)-furanyl-pterocarpan-3-ol (FPC) on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen (TAM), on the growth of estrogen receptor-dependent breast cancer T47D cells. Methods The proliferation effect of FPC were conducted on T47D cells in vitro by MTT test. T47D cells were treated with FPC alone (0.01-200 µmol/L) or in combination with TAM 20 nmol/L. Furthermore, the expression of ER? or c-Myc were also determined by immunohistochemistry. Results The results indicated that administration of an anti-estrogen TAM showed growth inhibitory effect on T47D cells, wheraes co-administered with low concentration (less than 1 µmol/L) of FPC attenuated to promote cell proliferation. In contrast, the combination of TAM with higher doses (more than 20 µmol/L) of FPC showed growth inhibitory. This result was supported by immunocytochemistry studies that the administration of 20 nmol/L TAM down-regulated ER-? and c-Myc, but the combination of 20 nmol/L TAM and 1 µmol/L FPC robustly up-regulated expression of ER-?. Thus, the reduced growth inhibition of TAM 20 nmol/L by FPC 1 µmol/L on T47D cells may act via the modulation of ER-?. Conclusions The findings indicate and suggest that FPC had estrogenic activity at low concentrations and anti-estrogenic effect that are likely to be regulated by c-Myc and estrogen receptors. We also confirm that low concentration of FPC attenuated the growth-inhibitory effects of TAM on mammary tumor prevention. Therefore, the present study suggests that caution is warranted regarding the consumption of dietary FPC by breast cancer patients while on TMA therapy.

Nurrochmad, Arief; Lukitaningsih, Endang; Monikawati, Ameilinda; Septhea, Dita Brenna; Meiyanto, Edy

2013-01-01

35

Human endogenous retrovirus expression and reverse transcriptase activity in the T47D mammary carcinoma cell line.  

PubMed Central

We have examined the human mammary tumor cell line T47D and have found that these cells produce virus-like particles which band at the typical density for retroviral particles on a sucrose gradient, possess reverse transcriptase activity, and package HERV-K10-like sequences. Using this information and a bacterial expression system to identify long open reading frames, we have identified individual clones which have full-length open reading frames for reverse transcriptase and RNase H and which could encode the reverse transcriptase activity detected in these cells.

Patience, C; Simpson, G R; Colletta, A A; Welch, H M; Weiss, R A; Boyd, M T

1996-01-01

36

Presenilin 1\\/ -Secretase Is Associated with Cadmium-Induced E-Cadherin Cleavage and COX2 Gene Expression in T47D Breast Cancer Cells  

Microsoft Academic Search

Cadmium is a heavy metal that has multiple toxic effects on human health and has been classified as a human carcinogen. E-cadherin is a major target of cadmium; however, the roles of E-cadherin and cadmium and the mechanisms of tumor pro- gression remain to be defined. Here, we demonstrate that cadmium increases E-cadherin processing via a g-secretase in the T47D

Chang Seok Park; Ohn Soon Kim; Sang-Moon Yun; Sangmee A. Jo; Inho Jo; Young Ho Koh

2008-01-01

37

Relationship between internalization and calcitonin-induced receptor loss in T 47D cells  

Microsoft Academic Search

Exposure of T 47D human breast cancer cells to salmon calcitonin (sCT) resulted in a reduction of binding capacity for (¹²⁵I)iodo-sCT in washed cells. The reduction was both time and concentration dependent. Recovery of binding capacity in CT-pretreated T 47D cells occurred in the absence of CT, but was prevented by inhibitors of protein synthesis. Studies were carried out to

D. M. Findlay; T. J. Martin

1984-01-01

38

Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.  

PubMed

Introduction : Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods : The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results : Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion : The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy. PMID:23878789

Ebrahimnezhad, Zohreh; Zarghami, Nosratollah; Keyhani, Manoutchehr; Amirsaadat, Soumaye; Akbarzadeh, Abolfazl; Rahmati, Mohammad; Mohammad Taheri, Zohreh; Nejati-Koshki, Kazem

2013-05-23

39

Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.  

PubMed

Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10 ?M Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's 't' test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80-90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50-60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs alone. Proellex inhibited mRNA and protein levels of PR-B, reduced PRB/p300 complex formation in the nuclei and significantly reduced EGFR expression in T47Darom cells. Our results in the present study indicate that antiproliferative effect of Proellex is probably due to PR-B/EGFR modulation in ER+PR+, aromatase expressing cells. Overall these results suggest that antiprogestin, Proellex can be developed as a possible treatment strategy for aromatase overexpressing ER+/PR+ breast cancer patients as well as for aromatase inhibitor resistant breast cancer patients. PMID:22939887

Gupta, Akash; Mehta, Rajeshwari; Alimirah, Fatouma; Peng, Xinjian; Murillo, Genoveva; Wiehle, Ronald; Mehta, Rajendra G

2012-08-23

40

PI3K/Akt-sensitive MEK-independent compensatory circuit of ERK activation in ER-positive PI3K-mutant T47D breast cancer cells  

PubMed Central

We explored the crosstalk between cell survival (phosphatidylinositol 3-kinase (PI3K)/Akt) and mitogenic (Ras/Raf/MEK/extracellular signal-regulated kinase (ERK)) signaling pathways activated by an epidermal growth factor (EGF) and analyzed their sensitivity to small molecule inhibitors in the PI3K-mutant estrogen receptor (ER)-positive MCF7 and T47D breast cancer cells. In contrast to MCF7 cells, ERK phosphorylation in T47D cells displayed resistance to MEK inhibition by several structurally different compounds, such as U0126, PD 098059 and PD 198306, MEK suppression by small interfering RNA (siRNA) and was also less sensitive to PI3K inhibition by wortmannin. Similar effect was observed in PI3K-wild type ER-positive BT-474 cells, albeit to a much lesser extent. MEK-independent ERK activation was induced only by ErbB receptor ligands and was resistant to inhibition of several kinases and phosphatases that are known to participate in the regulation of Ras/mitogen-activated protein kinase (MAPK) cascade. Although single agents against PDK1 or Akt did not affect EGF-induced ERK phosphorylation, a combination of PI3K/Akt and MEK inhibitors synergistically suppressed ERK activation and cellular growth. siRNA-mediated silencing of class I PI3K or Akt1/2 genes also significantly decreased U0126-resistant ERK phosphorylation. Our data suggest that in T47D cells ErbB family ligands induce a dynamic, PI3K/Akt-sensitive and MEK-independent compensatory ERK activation circuit that is absent in MCF7 cells. We discuss candidate proteins that can be involved in this activation circuitry and suggest that PDZ-Binding Kinase/T-LAK Cell-Originated Protein Kinase (PBK/TOPK) may play a role in mediating MEK-independent ERK activation.

Aksamitiene, Edita; Kholodenko, Boris N.; Kolch, Walter; Hoek, Jan B.; Kiyatkin, Anatoly

2010-01-01

41

Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor ? in T47D breast cancer cells  

Microsoft Academic Search

Potential interactions between prolactin (PRL) and estradiol (E2) in breast cancer cells were explored by examining the effect\\u000a of PRL on estrogen receptor (ER) serine-118 phosphorylation, ER down-regulation, and E2-stimulated cell proliferation. Both\\u000a E2 and PRL resulted in prolonged ER? serine-118 phosphorylation, but used different signaling pathways to achieve this end.\\u000a Both hormones also decreased the amount of ER?, but

YenHao Chen; KuangTzu Huang; KuanHui E. Chen; Ameae M. Walker

2010-01-01

42

Human Endogenous Retrovirus (HERV-K) Reverse Transcriptase as a Breast Cancer  

Microsoft Academic Search

A reverse transcriptase (RT) cDNA, designated HERV-K-T47D-RT, was isolated from a hormonally treated human breast cancer cell line. The protein product putative sequence is 97% identical to the human endogenous HERV-K retroviral sequences. Recombinant T47D-RT protein was used to generate polyclonal antibodies. The expression of HERV-K-T47D-RT protein increased in T47D cells after treatment with estrogen and progesterone. The RT-associated DNA

Maya Golan; Amnon Hizi; James H. Resau; Hadar Reichman; Iafa Keydarand; Ilan Tsarfaty

2008-01-01

43

Effects of zearalenone and ?-Zearalenol in comparison with Raloxifene on T47D cells  

PubMed Central

Zearalenone (Zen) is a mycotoxin with estrogenic effect which contaminates cereals. In cell culture, Zen and its metabolite, ?-Zearalenol (?-Zel), stimulate breast cancer cells growth. Today hormone-dependent cancers are important because of high incidence and death rate. Previous studies showed that Zen and ?-Zel have an effect on hormone-dependent cancers. This study explains the effects of the mentioned compounds in comparison with Raloxifene as an anti-estrogen. Cell culture technique was used with MDA-MB-231 and T47D cells for evaluation of compounds. MDA-MB-231 cells were used as negative control and also for proving that treatment compounds merely affect, due to their proliferation activity in the applied doses. According to the Resazurine-based method, for toxicity assay, none of the test compounds have an effect on MDA-MB-231 cells but do effect the growth of T47D cells. Zen and ?-Zel at low concentrations (10–8–10–9 M) stimulated T47D cell growth and Raloxifene strongly inhibited cell growth induced by Zen and ?-Zel. There is a noticeable result in controlling diet of hormonal carcinogenic compounds and applying novel anti-estrogens for prevention and treatment of hormone-dependent cancers.

Khosrokhavar, Roya; Rahimifard, Nahid; Shoeibi, Shahram; Hamedani, Morteza Pirali; Hosseini, Mir-Jamal

2009-01-01

44

Differential steroid hormone regulation of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) in breast cancer cell lines  

Microsoft Academic Search

We have investigated the steroid hormone regulation of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) in the breast cancer cell lines BT-474, T-47D, MFM-223, MCF-7, ZR-75-1, MDA-MB-435, and BT-20. Using highly sensitive time-resolved fluorometric immunoassays, we were able to detect significant amounts of both kallikreins in tissue culture supernatants of BT-474, T-47D, and MFM-223 cells after hormonal stimulation. However,

Angeliki Magklara; Linda Grass; Eleftherios P. Diamandis

2000-01-01

45

METABOLITES OF BENZO[A]FLUORANTHENE ARE POTENT CYP1 INDUCERS IN T-47D HUMAN BREAST CANCER CELLS. (R827180)  

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

46

Phytoestrogen-mediated inhibition of proliferation of the human T47D breast cancer cells depends on the ER?\\/ER? ratio  

Microsoft Academic Search

This study investigates the importance of the intracellular ratio of the two estrogen receptors ER? and ER? for the ultimate potential of the phytoestrogens genistein and quercetin to stimulate or inhibit cancer cell proliferation. This is of importance because (i) ER? has been postulated to play a role in modulating ER?-mediated cell proliferation, (ii) genistein and quercetin may be agonists

A. M. Sotoca; D. Ratman; P. van der Saag; A. Ström; J. A. Gustafsson; J. J. M. Vervoort; I. M. C. M. Rietjens; A. J. Murk

2008-01-01

47

Induction of differentiation by 1?-hydroxyvitamin D 5 in T47D human breast cancer cells and its interaction with vitamin D receptors  

Microsoft Academic Search

The role of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), in cell differentiation is well established. However, its use as a differentiating agent in a clinical setting is precluded due to its hypercalcaemic activity. Recently, we synthesised a relatively non-calcaemic analogue of vitamin D5, 1?-hydroxyvitamin D5 (1?(OH)D5), which inhibited the development of carcinogen-induced mammary lesions in culture

G Lazzaro; A Agadir; W Qing; M Poria; R. R Mehta; R. M Moriarty; T. K Das Gupta; X.-K Zhang; R. G Mehta

2000-01-01

48

Modulation of laminin receptor expression by estrogen and progestins in human breast cancer cell lines.  

PubMed

The effects of estradiol and two synthetic progestins (ORG2058 and R5020) on the expression of the high-affinity, metastasis-associated laminin receptor in two human breast carcinoma cell lines were examined. The T47D cell line contains estrogen and progesterone receptors, but the MDA-MB 231 cell line lacks both receptors. Treatment of T47D cells with 10(-9) M estradiol alone results in a three-fold increase (P less than or equal to .05) in the steady-state level of laminin receptor mRNA determined by RNA blot analysis as well as in cell-surface, laminin receptor expression that is evaluated by immunofluorescence. No effects of estradiol on the receptor-negative MDA-MB 231 cells were observed. Untreated and steroid-treated MDA-MB 231 cells had higher levels of laminin receptor mRNA than did untreated or estradiol-treated T47D cells. A more dramatic increase (five-fold; P less than or equal to .005) of mRNA and cell-surface expression in T47D cells was observed after treatment with estradiol plus 10(-8) M progestin or with progestin alone. Estradiol treatment also increased chemotaxis and haptotaxis of T47D cells but not of MDA-MB 231 cells to laminin; it had no effect on the attachment of these latter cells to laminin. Interestingly, treatment with estradiol plus progestin or progestin alone significantly increased the attachment of T47D cells to laminin but did not have an effect on either haptotaxis or chemotaxis to laminin. These results suggest that the various cell-laminin interactions are mediated by different mechanisms. The augmentation of laminin receptor mRNA by estrogen and progesterone treatment in hormone receptor-positive cells, but not in cells that lack these receptors, may relate functionally to the difference in the clinical aggressiveness between classes of breast cancers. PMID:2523976

Castronovo, V; Taraboletti, G; Liotta, L A; Sobel, M E

1989-05-10

49

Inhibitory effects of Indole3-carbinol on invasion and migration in human breast cancer cells  

Microsoft Academic Search

Indole-3-carbinol (I3C) is a promising phytochemical agent in chemoprevention of breast cancer. Our present study is the first description of I3C that significantly inhibits the cell adhesion, spreading and invasion associated with an up-regulation of PTEN (a tumor suppressor gene) and E-cadherin (a regulator of cell–cell adhesion) expression in T47-D human breast cancer cells. Therefore, I3C exhibits anti-cancer activities by

Qinghui Meng; Itzhak D. Goldberg; Eliot M. Rosen; Saijun Fan

2000-01-01

50

Protein Kinase C? Expression Confers Retinoic Acid Sensitivity on MDA-MB-231 Human Breast Cancer Cells  

Microsoft Academic Search

Retinoic acid activation of retinoic acid receptor ? (RAR?) induces protein kinase C? (PKC?) expression and inhibits proliferation of the hormone-dependent T-47D breast cancer cell line. Retinoic acid has no effect on proliferation or PKC? expression in a hormone-independent, breast cancer cell line (MDA-MB-231). To test the role of PKC? in retinoic acid-induced growth arrest of human breast cancer cells

Yunhi Cho; David A. Talmage

2001-01-01

51

Structure-dependent Induction of Aryl Hydrocarbon Hydroxylase in Human Breast Cancer Cell Lines and Characterization of the Ah Receptor1  

Microsoft Academic Search

The structure-dependent induction of aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase by 2,3,7,8-tetrachlorodibenzo- p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, and 1,2,4,7,8-pentachlorodi- benzo-p-dioxin was determined in the MCF-7, T47-D, and MDA-MB- 231 human breast cancer cell lines. Both the MCF-7 and T47-D cells were responsive to the induction effects of the halogenated aryl hydro carbons and the structure-induction relationships were comparable to the reported structure-activity

M. Harris; J. Piskorska-Pliszczynska; T. Zacharewski; M. Romkes; S. Safe

52

Retinoids arrest breast cancer cell proliferation: retinoic acid selectively reduces the duration of receptor tyrosine kinase signaling  

Microsoft Academic Search

Retinoic acid (RA) induces cell cycle arrest of hormone-dependent human breast cancer (HBC) cells. Previously, we demonstrated that RA-induced growth arrest of T-47D HBC cells required the activity of the RA-induced protein kinase, protein kinase C? (PKC?) [J. Cell Physiol. 172 (1997) 306]. Here, we demonstrate that RA treatment of T-47D cells interfered with growth factor signaling to downstream, cytoplasmic

Ann P. Tighe; David A. Talmage

2004-01-01

53

Lactate Dehydrogenase-B Is Silenced by Promoter Methylation in a High Frequency of Human Breast Cancers  

PubMed Central

Objective Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer. Experimental design Lactate Dehydrogenase (LDH) isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA. Results Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/ 25 cases of breast cancer tissues, but not in 5/ 5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained), was seen in 23/ 26 (88%) breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O2), for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p?=?0.002), and T-47D cells (2.9 fold, p?=?0.009), but not in MDA-MB-436 (-0.9 fold, p?=?0.229), or MCF10AT (1.2 fold, p?=?0.09) cells. Conclusions Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia.

Brown, Nicola J.; Higham, Sue E.; Perunovic, Branko; Arafa, Mohammad; Balasubramanian, Sabapathy; Rehman, Ishtiaq

2013-01-01

54

Coexistence of novel amylin-binding sites with calcitonin receptors in human breast carcinoma MCF7 cells  

Microsoft Academic Search

Amylin, calcitonin (CT) and calcitonin gene-related peptide (CGRP) share limited structural homology including amino-terminal ring structures linked by a disulfide bridge and amidated carboxy-termini. Here, we have compared (125I)Bolton-Hunter-(Lys1) rat amylin ((125I)amylin) binding and the stimulation of cyclic AMP accumulation by human (h) amylin, hCT and hCGRP-I in the human breast carcinoma cell lines MCF-7 and T47D, which predominantly express

U Zimmermann; B Fluehmann; W Born; J A Fischer; R Muff

1997-01-01

55

type I and retinoic acid receptors a2, 32, and y2 in human breast cancer cells  

Microsoft Academic Search

Because the retinoic acid (RA) signal- ing pathway regulates cell proliferation and differen- tiation, inactivation of genes integral to the pathway represents a potential mechanism of carcinogenesis. We have studied in human breast cancer cells (T47D, MCF-7, ZR75-1, MDA-MB-231, and BT2O) the ex- pression of a subset of retinoid signaling genes that are themselves transcriptionally up-regulated by HA, the cellular

YONGKUI JING; JIE ZHANG; IRA J. BLEIWEISS; SAMUEL WAXMAN; ARTHUR ZELENT; RAFAEL MIRA-Y-LOPEZ

56

INDUCTION OF CYP1A1 AND CYP1B1 IN T-47D HUMAN BREAST CANCER CELLS BY BENZO[A]PYRENE IS DIMINISHED BY ARSENITE. (R827180)  

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

57

EFFECTS OF BENZO[A]PYRENE AND ARSENITE ON CYP1A1 AND CYP1B1 MRNA LEVELS IN T-47D HUMAN BREAST CANCER CELLS: DETERMINATION BY A BRANCHED DNA ASSAY. (R827180)  

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

58

In vitro studies of tibolone in breast cells  

Microsoft Academic Search

Objective: To investigate the effects of tibolone and its main metabolites on breast homeostasis.Design: In vitro studies in primary cultures of normal breast cells and in breast cancer cell lines.Setting: Hospital-based academic research center.Patient(s): Human breast cells were obtained from women undergoing surgery for hypermastia. Breast cancer cell lines (MCF-7, T47-D, and ZR75-1) were routinely obtained from subcultures.Intervention(s): Cells were

Anne Gompel; Marc Chaouat; Denis Jacob; Jean-Yves Perrot; Helenius J Kloosterboer; William Rostene

2002-01-01

59

Glyphosate induces human breast cancer cells growth via estrogen receptors.  

PubMed

Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10(-12) to 10(-6)M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ER? and ? expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. PMID:23756170

Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

2013-06-10

60

Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin  

PubMed Central

We have investigated the production, growth and inactivation of gastrin-releasing peptide (GRP)-like peptides in human breast cancer cell lines. Radioimmunoassay detected GRP-like immunoreactivity (GRP-LI) in T47D breast cancer cells but not in the conditioned medium, indicating rapid clearance. No GRP-LI was found in the ZR-75-1 or MDA-MB-436 cells or their conditioned medium. High-performance liquid chromatography (HPLC) analysis of the GRP-LI in the T47D cells revealed a major peak, which co-eluted with GRP18–27, and a minor more hydrophilic peak. In vitro stimulation of T47D cell growth by bombesin (BN) was enhanced to 138% of control levels (bombesin alone) by the addition of the selective endopeptidase EC 3.4.24.11 inhibitor phosphoramidon (0.1 ng ml?;1). Fluorogenic analysis using whole cells confirmed low levels of this phosphoramidon-sensitive enzyme on the T47D cells. This enzyme, previously unreported in human breast cancer cells, significantly modulates both T47D growth and its response to BN-induced growth. © 1999 Cancer Research Campaign

Burns, D M; Walker, B; Gray, J; Nelson, J

1999-01-01

61

Prostaglandin E2 production and metabolism in human breast cancer cells and breast fibroblasts. Regulation by inflammatory mediators.  

PubMed Central

Malignant human breast tumours contain high levels of prostaglandin E2 (PGE2). However, the mechanisms controlling PGE2 production in breast cancer are unknown. This in vitro study investigates the capacity for PGE2 synthesis and metabolism in several human breast cancer cell lines and early passage human breast fibroblasts and seeks to identify potential regulatory factors which may control these pathways. Basal PGE2 production rose up to 30-fold in breast fibroblast lines on addition of exogenous arachidonic acid (10 microM), whereas no such changes were observed in six out of seven cancer cell lines, with the exception of modest increases in MDA-MB-231 cells. Interleukin 1 beta (IL-1 beta) also induced PGE2 production in breast fibroblasts in the presence of excess substrate, consistent with cyclo-oxygenase induction by the cytokine. Under these conditions only Hs578T cells and MDA-MB-231 cells demonstrated large increases in PGE2 in response to IL-1 beta or phorbol ester; no such responses were seen in MCF-7, T47-D, ZR-75-1, BT-20 or CLF-90-1 cells. In the absence of added arachidonate, bradykinin (BK) and endothelin-1 (ET-1), potentiated PGE2 production in IL-1 beta-treated fibroblasts, possibly by mobilising endogenous substrate. PGE2 also stimulated ET-1 production by breast cancer cells. In co-cultures with T47-D cells both basal and stimulated PGE2 production by breast fibroblasts was greatly reduced. This appeared to be due to metabolic inactivation by the cancer cell since T47-D cells readily converted PGE2 to 15-keto-PGE2. This apparent 15-hydroxy-PG dehydrogenase activity was stimulated by TPA and inhibited by cycloheximide. In conclusion, breast fibroblasts, particularly under the influence of inflammatory mediators, provide a potentially rich source for PGE2 production in breast tumours, whereas significant contributions from the epithelial tumour component may be restricted to cancer cells exhibiting an invasive phenotype. Metabolic inactivation by the cancer cells may also play an important role in the regulation of breast tumour PGE2 levels.

Schrey, M. P.; Patel, K. V.

1995-01-01

62

Regulation of Agonist--and Antagonist--Mediated Activation of Human Progesterone Receptors by Phosphorylation.  

National Technical Information Service (NTIS)

The human progesterone receptor (hPR) in breast cancer cells (T47D) is phosphorylated on multiple serine residues. I have previously reported the identification of eight phosphorylation sites. Here I show the identification of a new site, Ser2O. This site...

Y. Zhang

1996-01-01

63

Conjugated Linoleic Acid (CLA) inhibits expression of the Spot 14 (THRSP) and fatty acid synthase genes and impairs the growth of human breast cancer and liposarcoma cells  

PubMed Central

Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes required for fatty acid synthesis in normal and malignant mammary epithelial and adipose cells. Havartine and Bauman reported that conjugated linoleic acid (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues, and reduces milk fat production in cows. We hypothesized that CLA inhibits S14 gene expression in human breast cancer and liposarcoma cells, and that this will retard their growth. Exposure of T47D breast cancer cells to a mixture of CLA isomers reduced the expression of the S14 and fatty acid synthase (FAS) genes. The mixture caused a dose-related inhibition of T47D cell growth, as did pure c9, t11- and t10, c12-CLA, but not linoleic acid. Similar effects were observed in MDA-MB-231 breast cancer cells. Provision of 8 ?M palmitate fully (CLA mix, t10, c12-CLA) or partially (c9, t11-CLA) reversed the antiproliferative effect in T47D cells. CLA likewise suppressed levels of S14 and FAS mRNAs in liposarcoma cells, and caused growth inhibition that was prevented by palmitic acid. CLA did not affect the growth of nonlipogenic HeLa cells or human fibroblasts. We conclude that, as in bovine mammary and mouse adipose cells, CLA suppresses S14 and FAS gene expression in human breast cancer and liposarcoma cells. Rescue from the antiproliferative effect of CLA by palmitic acid indicates that reduced tumor lipogenesis is a major mechanism for the anticancer effects of CLA.

Donnelly, Christina; Olsen, Arne M.; Lewis, Lionel D.; Eisenberg, Burton L.; Eastman, Alan; Kinlaw, William B.

2010-01-01

64

Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis  

Microsoft Academic Search

Classical steroid mode of action involves binding to intracellular receptors, the later acting as ligand-activated nuclear transcription factors. Recently, membrane sites for different steroids have been also identified, mediating rapid, non-genomic, steroid actions. Membrane sites for estrogen and androgen have been found in a number of different cell types, bearing or not classical intracellular receptors. In the present study, with

Marilena Kampa; Artemissia-Phoebe Nifli; Ioannis Charalampopoulos; Vassilia-Ismini Alexaki; Panayiotis A. Theodoropoulos; Efstathios N. Stathopoulos; Achille Gravanis; Elias. Castanas

2005-01-01

65

Prodigiosin, the red pigment of Serratia marcescens, shows cytotoxic effects and apoptosis induction in HT-29 and T47D cancer cell lines.  

PubMed

In this study, a red pigment of Serratia marcescens PTCC 1111 was purified and identified for antiproliferative activities in HT-29 and T47D cancer cell lines. (1)H-NMR spectroscopy and LC/MS analysis confirmed prodigiosin structure. The antiproliferative effects of prodigiosin were determined by employing the MTT assay. The changes in cell cycle pattern were studied with 4',6-diamidino-2-phenylindole (DAPI) reagent using flow cytometry assay, and Annexin V-PI method was used for apoptotic analysis. Results of MTT assay showed that HT-29 cells were more sensitive to prodigiosin than T47D cells. Prodigiosin-treated HT-29 cells showed increase in S phase and decrease in G2/M, but treated T47D cells showed cell cycle pattern relatively similar to Roswell Park Memorial Institute medium (RPMI). Apoptotic effect of prodigiosin was higher than doxorubicin in HT-29 cells. The data reported here indicate that prodigiosin is a promising antineoplastic agent that triggers apoptosis in different cancer cell lines. PMID:21985476

Dalili, D; Fouladdel, Sh; Rastkari, N; Samadi, N; Ahmadkhaniha, R; Ardavan, A; Azizi, E

2011-10-10

66

Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT5 activation in breast cancer cells in vitro  

Microsoft Academic Search

Two recent papers demonstrate that prolactin plays an important role in the induction and progression of mammary tumours. Retinoids have been shown to be potent inhibitors of breast carcinogenesis. We studied expression of prolactin receptor mRNA in human breast cancer cell lines MCF-7, SKBR-3, T47D and BT-20 treated with and without retinoids using Northern blot and a quantitative polymerase chain

M Widschwendter; A Widschwendter; T Welte; G Daxenbichler; A G Zeimet; A Bergant; J Berger; J-P Peyrat; S Michel; W Doppler; C Marth

1999-01-01

67

Progestin-dependent progression of human breast tumor xenografts: a novel model for evaluating antitumor therapeutics.  

PubMed

Recent clinical trials indicate that synthetic progestins may stimulate progression of breast cancer in postmenopausal women, a result that is consistent with studies in chemically-induced breast cancer models in rodents. However, progestin-dependent progression of breast cancer tumor xenografts has not been shown. This study shows that xenografts obtained from BT-474 and T47-D human breast cancer cells without Matrigel in estrogen-supplemented nude mice begin to regress within days after tumor cell inoculation. However, their growth is resumed if animals are supplemented with progesterone. The antiprogestin RU-486 blocks progestin stimulation of growth, indicating involvement of progesterone receptors. Exposure of xenografts to medroxyprogesterone acetate, a synthetic progestin used in postmenopausal hormone replacement therapy and oral contraception, also stimulates growth of regressing xenograft tumors. Tumor progression is dependent on expression of vascular endothelial growth factor (VEGF); growth of progestin-dependent tumors is blocked by inhibiting synthesis of VEGF or VEGF activity using a monoclonal anti-VEGF antibody (2C3) or by treatment with PRIMA-1, a small-molecule compound that reactivates mutant p53 into a functional protein and blocks VEGF production. These results suggest a possible model system for screening potential therapeutic agents for their ability to prevent or inhibit progestin-dependent human breast tumors. Such a model could potentially be used to screen for safer antiprogestins, antiangiogenic agents, or for compounds that reactivate mutant p53 and prevent progestin-dependent progression of breast disease. PMID:17942925

Liang, Yayun; Besch-Williford, Cynthia; Brekken, Rolf A; Hyder, Salman M

2007-10-15

68

Growth-inhibitory effects of CD40 ligand (CD154) and its endogenous expression in human breast cancer.  

PubMed

CD40 binding produces multifaceted growth signals in normal and malignant B cells, whereas its physiological role is less well characterized in epithelial cancers. We examined the growth outcome of CD40 ligation in human breast cancer cells, using CD40+ (T47D and BT-20) and CD40-negative (MCF-7, ZR-75-1) cell lines as defined by flow cytometric analysis, immunohistochemistry, and reverse transcription-PCR. Treatment with the soluble recombinant CD40 ligand (CD40L) molecules gp39 or CD40L-trimer significantly reduced [3H]thymidine uptake in BT-20 and T47D cells by up to 40%, but did not affect the growth of CD40-negative MCF-7 or ZR-75-1 cells. Similarly, significant growth inhibition was observed after co-incubation with CD40L-transfected murine L cells (55.0 +/- 8.9%, P < 0.001) that express membrane CD40L constitutively, or with paraformaldehyde-fixed, CD3+ CD40L+ PBLs from three different HLA-mismatched donors (39.7 +/- 3.7%, P < 0.01). Untransfected L cells and non-CD40L-expressing lymphocytes did not produce significant growth inhibition. The in vivo antitumorigenic effects of CD40L were examined using a s.c. severe combined immunodeficient-hu xenograft model. Pretreatment with two different soluble recombinant CD40L constructs (CD40L and gp39) produced similar xenograft growth-inhibitory effects [67 +/- 24% (n = 4), and 65 +/- 14% (n = 8) inhibition, respectively], which were reversed by co-treatment with the CD40L-neutralizing antibody LL48. In vitro analysis indicated that CD40L-induced growth inhibition was accompanied by apoptotic events including cell shrinkage, rounding, and detachment from the adherent T47D culture monolayer. Thirty-one and 27% of gp39-treated T47D and BT-20 cells underwent apoptosis, respectively, as compared with 56 and 65% from the same cell lines after treatment with the Fas agonistic antibody CH-11. An up-regulation of the proapoptotic protein Bax in T47D and BT-20 cells was observed, which indicated that this Bcl-2 family member may contribute to this growth-inhibitory effect. To explore the clinical relevance of CD40L-CD40 interaction, retrospective immunohistochemical analysis was carried to characterize in situ CD40- and CD40L-expression in breast cancer patient biopsies. All of the infiltrating ductal (5 of 5 cases tested) and lobular (4 of 4 cases) breast carcinomas, carcinomas in situ (6 of 6 cases), and mucinous carcinoma tested (1 case) expressed CD40. Varying proportions of tumor cells also expressed CD40L in the majority of infiltrating ductal (3 of 5 cases) and lobular (3 of 4 cases) carcinomas, and carcinomas in situ (4 of 6 cases), as determined by immunohistochemistry and validated by RT-PCR detection of the CD40L message in only CD40L positive-staining cases. Tumor infiltrating mononuclear cells from infiltrating carcinomas and carcinomas in situ expressed CD40 (10 of 10 cases), but less commonly CD40L (1 case of infiltrating lobular carcinoma, 2 cases of carcinoma in situ). Our findings indicate that the CD40 signaling pathway is active in human breast carcinoma cells. However, tumor-infiltrating lymphocytes from primary tumor tissues may be limited in their capacity to directly modulate tumor growth through the CD40L-CD40 loop. PMID:11297266

Tong, A W; Papayoti, M H; Netto, G; Armstrong, D T; Ordonez, G; Lawson, J M; Stone, M J

2001-03-01

69

Structures and Mechanisms of Antitumor Agents - Xestoquinones Uncouple Cellular Respiration and Disrupt HIF Signaling in Human Breast Tumor Cells  

PubMed Central

The organic extract of a marine sponge Petrosia alfiani selectively inhibited iron chelator-induced hypoxia-inducible factor-1 (HIF-1) activation in a human breast tumor T47D cell-based reporter assay. Bioassay-guided fractionation yielded seven xestoquinones (1 – 7) including three new compounds 14-hydroxymethylxestoquinone (1), 15-hydroxymethylxestoquinone (2), and 14,15-dihydroxestoquinone (3). Compounds 1 – 7 were evaluated for their effects on HIF-1 signaling, mitochondrial respiration, and tumor cell proliferation/viability. The known metabolites adociaquinones A (5) and B (6), that possess a 3,4-dihydro-2H-1,4-thiazine-1,1-dioxide moiety, potently and selectively inhibited iron chelator-induced HIF-1 activation in T47D cells, each with an IC50 value of 0.2 ?M. Mechanistic studies revealed that adociaquinones promote oxygen consumption without affecting mitochondrial membrane potential. Compound 1 both enhances respiration and decreases mitochondrial membrane potential, suggesting that it acts as a protonophore that uncouples mitochondrial respiration.

Du, Lin; Mahdi, Fakhri; Datta, Sandipan; Jekabsons, Mika B.; Zhou, Yu-Dong; Nagle, Dale G.

2012-01-01

70

Structures and mechanisms of antitumor agents: xestoquinones uncouple cellular respiration and disrupt HIF signaling in human breast tumor cells.  

PubMed

The organic extract of a marine sponge, Petrosia alfiani, selectively inhibited iron chelator-induced hypoxia-inducible factor-1 (HIF-1) activation in a human breast tumor T47D cell-based reporter assay. Bioassay-guided fractionation yielded seven xestoquinones (1-7) including three new compounds: 14-hydroxymethylxestoquinone (1), 15-hydroxymethylxestoquinone (2), and 14,15-dihydroxestoquinone (3). Compounds 1-7 were evaluated for their effects on HIF-1 signaling, mitochondrial respiration, and tumor cell proliferation/viability. The known metabolites adociaquinones A (5) and B (6), which possess a 3,4-dihydro-2H-1,4-thiazine-1,1-dioxide moiety, potently and selectively inhibited iron chelator-induced HIF-1 activation in T47D cells, each with an IC(50) value of 0.2 ?M. Mechanistic studies revealed that adociaquinones promote oxygen consumption without affecting mitochondrial membrane potential. Compound 1 both enhances respiration and decreases mitochondrial membrane potential, suggesting that it acts as a protonophore that uncouples mitochondrial respiration. PMID:22938093

Du, Lin; Mahdi, Fakhri; Datta, Sandipan; Jekabsons, Mika B; Zhou, Yu-Dong; Nagle, Dale G

2012-08-31

71

Cyclin D2 activates Cdk2 in preference to Cdk4 in human breast epithelial cells  

Microsoft Academic Search

To investigate the possibility of differing roles for cyclins D1 and D2 in breast epithelial cells, we examined the expression, cell cycle regulation and activity of these two G1 cyclins in both 184 normal breast epithelial cells and T-47D breast cancer cells. Synchronisation studies in 184 cells demonstrated that cyclin D1 and cyclin D2 were differentially regulated during G1, with

Kimberley J Sweeney; Boris Sarcevic; Robert L Sutherland; Elizabeth A Musgrove

1997-01-01

72

Macrophages promote angiogenesis in human breast tumour spheroids in vivo  

PubMed Central

An in vivo model has been established to study the role of macrophages in the initiation of angiogenesis by human breast tumour spheroids in vivo. The extent of the angiogenic response induced by T47D spheroids implanted into the dorsal skinfold chamber in nude mice was measured in vivo and compared to that induced by spheroids infiltrated with human macrophages prior to implantation. Our results indicate that the presence of macrophages in spheroids resulted in at least a three-fold upregulation in the release of vascular endothelial growth factor (VEGF) in vitro when compared with spheroids composed only of tumour cells. The angiogenic response measured around the spheroids, 3 days after in vivo implantation, was significantly greater in the spheroids infiltrated with macrophages. The number of vessels increased (macrophages vs no macrophages 34±1.9 vs 26±2.5, P<0.01), were shorter in length (macrophages vs no macrophages 116±4.92 vs 136±6.52, P<0.008) with an increased number of junctions (macrophages vs no macrophages 14±0.93 vs 11±1.25, P<0.025) all parameters indicative of new vessel formation. This is the first study to demonstrate a role for macrophages in the initiation of tumour angiogenesis in vivo.

Bingle, L; Lewis, C E; Corke, K P; Reed, M W R; Brown, N J

2006-01-01

73

Human breast cancer cells contain a phosphoramidon-sensitive metalloproteinase which can process exogenous big endothelin-1 to endothelin-1: a proposed mitogen for human breast fibroblasts.  

PubMed Central

Endothelin-1 (ET-1) levels are elevated in human breast tumours compared with normal and benign tissues, and in the presence of insulin-like growth factor 1 (IGF-I) ET-1 is a potent mitogen for human breast fibroblasts. In this study we have examined the ability of intact human breast cancer cell lines to process exogenously added big ET-1 (1-38) to the active mature ET-1 peptide by using a specific radioimmunometric assay. In both hormome-dependent (MCF-7, T47-D) and hormone-independent (MDA-MB-231) breast cancer cell lines the putative endothelin-converting enzyme (ECE) exhibited apparent Michaelis-Menten kinetics when converting added big ET-1 to ET-1. Both basal ET-1 production and exogenously added big ET-1 to ET-1 conversion were greatly reduced in all three cell lines in response to the metalloproteinase inhibitor phosphoramidon but were insensitive to other classes of protease inhibitors. Inhibition was also observed when cells were incubated in the presence of the divalent cation chelators 1,10-phenanthroline and EDTA. In MCF-7 cells the optimal pH for the ECE activity using a saponin cell permeabilisation procedure was found to residue within a narrow range of 6.2-7.26. Our results indicate that human breast cancer cells contain a neutral phosphoramidon-sensitive metalloproteinase which can process big ET-1 to ET-1. In the breast this conversion could contribute substantially to the local extracellular levels of this proposed paracrine breast fibroblast mitogen.

Patel, K. V.; Schrey, M. P.

1995-01-01

74

Estrogen receptor-beta messenger RNA expression in human breast tumor biopsies: relationship to steroid receptor status and regulation by progestins.  

PubMed

When the level of estrogen receptor (ER)-beta mRNA in tumors, determined by reverse transcription-PCR, was assessed according to either ER status or PR status alone, determined by ligand binding assays, the level of ER-beta mRNA was significantly lower in PR+ tumors compared with PR- tumors (P = 0.036), and no association with ER status was found. Subgroup analysis showed that ER-beta mRNA expression in ER+/PR+ breast tumors was significantly less than in ER+/PR- (P = 0.009), ER-/PR+ (P = 0.029), and ER-/PR- (P = 0.023) groups. Interestingly, the ER-beta mRNA expression was specifically decreased by progestin in T47D breast cancer cells. The data suggest the possibility that expression of ER-beta in human breast tumors is a marker of endocrine therapy responsiveness. PMID:9973194

Dotzlaw, H; Leygue, E; Watson, P H; Murphy, L C

1999-02-01

75

Progesterone Receptor Inhibits Proliferation of Human Breast Cancer Cells via Induction of MAPK Phosphatase 1 (MKP-1/DUSP1)*  

PubMed Central

The roles of progesterone (P4) and of progesterone receptor (PR) in development and pathogenesis of breast cancer remain unclear. In this study, we observed that treatment of T47D breast cancer cells with progestin antagonized effects of fetal bovine serum (FBS) to stimulate cell proliferation, whereas siRNA-mediated knockdown of endogenous PR abrogated progestin-mediated anti-proliferative effects. To begin to define mechanisms for the anti-proliferative action of P4/PR, we considered the role of MAPK phosphatase 1 (MKP-1/DUSP1), which catalyzes dephosphorylation and inactivation of MAPKs. Progestin treatment of T47D cells rapidly induced MKP-1 expression in a PR-dependent manner. Importantly, P4 induction of MKP-1 was associated with reduced levels of phosphorylated ERK1/2, whereas siRNA knockdown of MKP-1 blocked progestin-mediated ERK1/2 dephosphorylation and repression of FBS-induced cell proliferation. The importance of PR in MKP-1 expression was supported by findings that MKP-1 and PR mRNA levels were significantly correlated in 30 human breast cancer cell lines. By contrast, no correlation was observed with the glucocorticoid receptor, a known regulator of MKP-1 in other cell types. ChIP and luciferase reporter assay findings suggest that PR acts in a ligand-dependent manner through binding to two progesterone response elements downstream of the MKP-1 transcription start site to up-regulate MKP-1 promoter activity. PR also interacts with two Sp1 sites just downstream of the transcription start site to increase MKP-1 expression. Collectively, these findings suggest that MKP-1 is a critical mediator of anti-proliferative and anti-inflammatory actions of PR in the breast.

Chen, Chien-Cheng; Hardy, Daniel B.; Mendelson, Carole R.

2011-01-01

76

Differential expression of WISP-1 and WISP-2 genes in normal and transformed human breast cell lines.  

PubMed

The transcriptional alterations of specific gene(s) are actively associated with the development of different cancers including breast. The preceding studies of different laboratories documented at least 40 genes that may contribute directly to the genesis of cancer. Using differential display, RT-PCR and DNA sequencing analyses in normal human mammary epithelial cells (HMEC) and various breast tumor cell lines including MCF-7, ZR-75, T-47D and SKBR2, we demonstrated that WISP-1 and WISP-2 genes are differentially transcribed in these cells. WISP-2 mRNA transcription was identified in all 4 tumor derived cell lines, but the mRNA expression was undetected or minimally detected in normal breast epithelial cells. WISP-1 mRNA expression was identified in normal and transformed cell lines. However, the level of expression was higher in different breast tumor cell lines as compared to HMEC. The mRNA expression profiles of WISP genes in normal breast epithelial cells and breast tumor derived cell lines indicated a strong possibility of the involvement of WISP-signaling in the development of human breast tumors, and can be utilized as genetic markers of this disease. PMID:11855747

Saxena, N; Banerjee, S; Sengupta, K; Zoubine, M N; Banerjee, S K

2001-12-01

77

Structural effects of TiO2 nanoparticles and doxorubicin on DNA and their antiproliferative roles in T47D and MCF7 cells.  

PubMed

The structural changes in DNA caused by the combined effects of TiO2 nanoparticles (TiO2 NPs) and doxorubicin (DOX) were investigated along with their corresponding inhibitory roles in the growth of T47D and MCF7 cells. The UV-visible titration studies showed that DOX+ TiO2 NPs could form a novel complex with DNA. The data also reveal that the TiO2-DOX complex forms through a 1:4 stoichiometric ratio in solution. The values of binding constants reveal that DOX+TiO2 NPs interact more strongly with DNA as compared to TiO2 NPs or DOX alone. CD data show that DOX+TiO2 NPs can noticeably cause disturbance on DNA structure compared to TiO2 NPs or DOX alone, considering that DNA is relatively thermally stable in the condition used. The anticancer property of 0.3 µM DOX+ 60 µM TiO2 NPs and 0.4 µM DOX+ 670 µM TiO2 NPs by MTT assay and DAPI stain demonstrates that this combination can tremendously diminish proliferation of T47D and MCF7cells compared to DOX or TiO2 NPs alone. The UV-Vis absorption spectroscopy, flow cytometry and fluorescence microscopy experiments show much more enhancement of DOX uptake through the use of TiO2 NPs. These results reveal that DOX+TiO2 NPs could proffer a novel strategy for the development of promising and efficient chemotherapy agents. PMID:23387974

Hekmat, Azadeh; Saboury, Ali Akbar; Divsalar, Adeleh; Seyedarabi, Arefeh

2013-07-01

78

Validation of T47D-KBluc cell assay for detection of estrogen receptor agonists and antagonists  

EPA Science Inventory

There is growing concern of exposure to fish, wildlife, and humans to environmental estrogens and their potential impact on reproductive health. Cell-based assays are useful tools to determine the estrogenic activity of chemicals. Confidence in in vitro assay results is strengthe...

79

Validation of T47D-KBluc cell assay for detection of estrogen receptor agonists and antagonists###  

EPA Science Inventory

There is growing concern of exposure to fish, wildlife, and humans to environmental estrogens and their potential impact on reproductive health. Cell-based assays are useful tools to determine the estrogenic activity of chemicals. Confidence in in vitro assay results is strengthe...

80

Role of ornithine decarboxylase in regulation of estrogen receptor alpha expression and growth in human breast cancer cells.  

PubMed

Our previous studies demonstrated that specific polyamine analogues, oligoamines, down-regulated the activity of a key polyamine biosynthesis enzyme, ornithine decarboxylase (ODC), and suppressed expression of estrogen receptor alpha (ER?) in human breast cancer cells. However, the mechanism underlying the potential regulation of ER? expression by polyamine metabolism has not been explored. Here, we demonstrated that RNAi-mediated knockdown of ODC (ODC KD) down-regulated the polyamine pool, and hindered growth in ER?-positive MCF7 and T47D and ER?-negative MDA-MB-231 breast cancer cells. ODC KD significantly induced the expression and activity of the key polyamine catabolism enzymes, spermine oxidase (SMO) and spermidine/spermine N (1)-acetyltransferase (SSAT). However, ODC KD-induced growth inhibition could not be reversed by exogenous spermidine or overexpression of antizyme inhibitor (AZI), suggesting that regulation of ODC on cell proliferation may involve the signaling pathways independent of polyamine metabolism. In MCF7 and T47D cells, ODC KD, but not DFMO treatment, diminished the mRNA and protein expression of ER?. Overexpression of antizyme (AZ), an ODC inhibitory protein, suppressed ER? expression, suggesting that ODC plays an important role in regulation of ER? expression. Decrease of ER? expression by ODC siRNA altered the mRNA expression of a subset of ER? response genes. Our previous analysis showed that oligoamines disrupt the binding of Sp1 family members to an ER? minimal promoter element containing GC/CA-rich boxes. By using DNA affinity precipitation and mass spectrometry analysis, we identified ZBTB7A, MeCP2, PARP-1, AP2, and MAZ as co-factors of Sp1 family members that are associated with the ER? minimal promoter element. Taken together, these data provide insight into a novel antiestrogenic mechanism for polyamine biosynthesis enzymes in breast cancer. PMID:22976807

Zhu, Qingsong; Jin, Lihua; Casero, Robert A; Davidson, Nancy E; Huang, Yi

2012-09-14

81

Regulation of human Cripto-1 expression by nuclear receptors and DNA promoter methylation in human embryonal and breast cancer cells.  

PubMed

Human Cripto-1 (CR-1) plays an important role in regulating embryonic development while also regulating various stages of tumor progression. However, mechanisms that regulate CR-1 expression during embryogenesis and tumorigenesis are still not well defined. In the present study, we investigated the effects of two nuclear receptors, liver receptor homolog (LRH)-1 and germ cell nuclear factor receptor (GCNF) and epigenetic modifications on CR-1 gene expression in NTERA-2 human embryonal carcinoma cells and in breast cancer cells. CR-1 expression in NTERA-2 cells was positively regulated by LRH-1 through direct binding to a DR0 element within the CR-1 promoter, while GCNF strongly suppressed CR-1 expression in these cells. In addition, the CR-1 promoter was unmethylated in NTERA-2 cells, while T47D, ZR75-1, and MCF7 breast cancer cells showed high levels of CR-1 promoter methylation and low CR-1 mRNA and protein expression. Treatment of breast cancer cells with a demethylating agent and histone deacetylase inhibitors reduced methylation of the CR-1 promoter and reactivated CR-1 mRNA and protein expression in these cells, promoting migration and invasion of breast cancer cells. Analysis of a breast cancer tissue array revealed that CR-1 was highly expressed in the majority of human breast tumors, suggesting that CR-1 expression in breast cancer cell lines might not be representative of in vivo expression. Collectively, these findings offer some insight into the transcriptional regulation of CR-1 gene expression and its critical role in the pathogenesis of human cancer. PMID:23129342

Bianco, Caterina; Castro, Nadia P; Baraty, Christina; Rollman, Kelly; Held, Natalie; Rangel, Maria Cristina; Karasawa, Hideaki; Gonzales, Monica; Strizzi, Luigi; Salomon, David S

2013-06-01

82

Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer  

PubMed Central

Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation.

Yu, Wei; Chai, Hongyan; Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue; Yang, Guifang; Cai, Xiaojun; Falck, John R.; Yang, Jing

2012-01-01

83

Immunologic analysis of human breast cancer progesterone receptors. 1. Immunonaffinity purification of transformed receptors and production of monoclonal antibodies  

SciTech Connect

A monoclonal antibody (MAb), designated PR-6, produced against chick oviduct progesterone receptors cross-reacts with the M/sub r/ 120,000 human B receptors. An immunomatrix prepared with PR-6 was used to purify progesterone receptors (PR) from T47D human breast cancer cells. Single-step immunoaffinity chromatography results in enrichment of B receptors (identified by immunoblot with PR-6 and by photoaffinity labeling with (/sup 3/H)promegestone) to a specific activity of 1915 pmol/mg of protein (or 23% purity) and with 27% yield. Purity and yields as judged by gel electrophoresis and densitometric scanning of the B protein were approximately 1.7-fold higher due to partial loss in hormone binding activity at the elution step. B receptors purified under these conditions are transformed and biologically active. They were maintained as undergraded 120-kDa doublets and retained both hormone and DNA binding activities. These purified B receptors were used as immunogen for production of four monoclonal antibodies against human PR. Three of the MAbs, designated as B-30 (IgG/sub 1/), B-64 (IgG/sub 1/), and B-11 (IgM), are specific for B receptors. The fourth MAb, A/B-52 (IgG/sub 1/), reacts with both A and B receptors. The IgG MAbs are monospecific for human PR since they recognize and absorb native receptor-hormone complexes, displace the sedimentation of 4S receptors on salt containing sucrose gradients, and, by immunoblot assay of crude T47D cytosol, react only with receptor polypeptides. Although mice were injected with B receptors only, production of A/B-52 which recognized both A and B receptors provides evidence that these two proteins share regions of structural homology.

Estes, P.A.; Suba, E.J.; Lawler-Heavner, J.; Elashry-Stowers, D.; Wei, L.L.; Toft, D.O.; Sullivan, W.P.; Horwitz, K.B.; Edwards, D.P.

1987-09-22

84

Estrogen Regulation of Thrombospondin-1 in Human Breast Cancer Cells  

PubMed Central

Expression of thrombospondin-1 (TSP-1), a large extracellular matrix protein, has been associated with modulation of angiogenesis and tumor growth. Both pro- and anti-angiogenic properties of TSP-1 have been described, and the role of TSP-1 expression in the growth and progression of human breast cancer is not clear. Because estrogens cause progression of many breast cancers, and estradiol (E2) downregulates a TSP-1 receptor, we examined whether TSP-1 is regulated by estrogen and involved in tumor progression. E2 induced TSP-1 expression in T47-D and MCF-7 breast cancer cells in vitro within 3-6 h; the induction was blocked by the anti-estrogen ICI 182,780, indicating that estrogen receptors (ER) are necessary for this effect. Furthermore, E2 caused the production of TSP-1 protein from tumor cells in an ER-alpha–dependent manner. The E2-mediated TSP-1 RNA induction was dose-dependent and blocked by actinomycin D, indicating that the response to E2 was at least partly transcriptional. Transfection studies with deletion constructs of the TSP-1 promoter identified an estrogen-responsive region in the human TSP-1 promoter, located between -2200 and -1792 bp upstream of the transcription start site. An antibody against TSP-1 restricted the proliferation of E2-dependent MCF-7 cells in vitro and in vivo. A panel of breast cancer cells proliferated in the presence of low concentrations of exogenous TSP-1, whereas higher concentrations inhibited proliferation. A real-time PCR analysis showed that E2 also induced TSP-1 mRNA in the normal mammary glands of immature ovariectomized mice in an ER-dependent manner. In summary, we report the novel observation that TSP-1 production is directly controlled by estrogens in ER-positive breast cancer cells, and the released protein has pro-growth regulatory functions. Consequently, we propose that TSP-1 could be a therapeutic target for anti-tumor therapy in early-stage tumors.

Hyder, Salman M; Liang, Yayun; Wu, Jianbo

2009-01-01

85

Interleukin 6 decreases cell-cell association and increases motility of ductal breast carcinoma cells  

PubMed Central

Treatment of transformed breast duct epithelial cells with IL-6 produces a unique cellular phenotype characterized by diminished proliferation and increased motility. Human ductal carcinoma cells (T- 47D and ZR-75-1 lines) are typically epithelioid in shape and form compact colonies in culture. Time-lapse cinemicrography shows that some untreated cells can transiently become fusiform or stellate in shape and separate from each other within a colony, but they usually rejoin their neighbors. While IL-6 suppresses the proliferation of these carcinoma cells, the IL-6-treated cells generally become stellate or fusiform and show increased motility. These changes persist as long as the cells are exposed to IL-6. This results in the dispersal of cells within colonies. The effects on cell growth, shape, and motility are reversible upon removal of IL-6. IL-6-treated T-47D cells display diminished adherens-type cell junctions, as indicated by markedly decreased vinculin-containing adhesions and intercellular desmosomal attachments. The effects on ZR-75-1 cell shape, colony number, and DNA synthesis are dependent on IL-6 concentration in the range from 0.15 to 15 ng/ml. Higher concentrations are required in T-47D cells for equivalent effects. Anti-IL-6 immune serum blocks IL-6 action. IL-6 represents a well-characterized molecule that regulates both the proliferation and junction-forming ability of breast ductal carcinoma cells.

1989-01-01

86

Combined Low Doses of PPAR? and RXR Ligands Trigger an Intrinsic Apoptotic Pathway in Human Breast Cancer Cells  

PubMed Central

Ligand activation of peroxisome proliferator-activated receptor (PPAR)? and retinoid X receptor (RXR) induces antitumor effects in cancer. We evaluated the ability of combined treatment with nanomolar levels of the PPAR? ligand rosiglitazone (BRL) and the RXR ligand 9-cis-retinoic acid (9RA) to promote antiproliferative effects in breast cancer cells. BRL and 9RA in combination strongly inhibit of cell viability in MCF-7, MCF-7TR1, SKBR-3, and T-47D breast cancer cells, whereas MCF-10 normal breast epithelial cells are unaffected. In MCF-7 cells, combined treatment with BRL and 9RA up-regulated mRNA and protein levels of both the tumor suppressor p53 and its effector p21WAF1/Cip1. Functional experiments indicate that the nuclear factor-?B site in the p53 promoter is required for the transcriptional response to BRL plus 9RA. We observed that the intrinsic apoptotic pathway in MCF-7 cells displays an ordinated sequence of events, including disruption of mitochondrial membrane potential, release of cytochrome c, strong caspase 9 activation, and, finally, DNA fragmentation. An expression vector for p53 antisense abrogated the biological effect of both ligands, which implicates involvement of p53 in PPAR?/RXR-dependent activity in all of the human breast malignant cell lines tested. Taken together, our results suggest that multidrug regimens including a combination of PPAR? and RXR ligands may provide a therapeutic advantage in breast cancer treatment.

Bonofiglio, Daniela; Cione, Erika; Qi, Hongyan; Pingitore, Attilio; Perri, Mariarita; Catalano, Stefania; Vizza, Donatella; Panno, Maria Luisa; Genchi, Giuseppe; Fuqua, Suzanne A.W.; Ando, Sebastiano

2009-01-01

87

Antiproliferative activity of L-asparaginase of Tetrahymena pyriformis on human breast cancer cell lines  

Microsoft Academic Search

Purified L-asparaginase of Tetrahymena pyriformis is a multi-subunit enzyme exhibiting protein kinase activity as well. The enzyme's L-asparaginase activity is affected by its phosphorylation state. Both native and dephosphorylated L-asparaginase show antiproliferative activity on three breast cancer cell lines (T47D, BT20 and MCF-7) and on Walker 256 cells. These cells do not possess measurable L-asparaginase or L-asparagine synthetase activity. When

D. A. Kyriakidis; S. A. E. Tsirka; I. K. Tsavdaridis; S. N. Iliadis; A. H. Kortsaris

1990-01-01

88

Development of an Androgen Reporter Gene Assay (AR-LUX) Utilizing a Human Cell Line with an Endogenously Regulated Androgen Receptor  

Microsoft Academic Search

The aim of the work described in this report is to develop and characterize a cell-based androgen reporter assay. For this purpose, the androgen receptor (AR) expressing human breast cancer cell line T47D was stably transfected with a luciferase gene under transcriptional control of the PB-ARE-2 androgen response element. The application of this cell line in an endogenous Androgen Receptor-mediated

B. M. G. Blankvoort; E. M. de Groene; A. P. van Meeteren-Kreikamp; R. F. Witkamp; R. J. T. Rodenburg; J. M. M. J. G. Aarts

2001-01-01

89

The low-toxicity 9-cis UAB30 novel retinoid down-regulates the DNA methyltransferases and has anti-telomerase activity in human breast cancer cells.  

PubMed

Retinoic acids and their derivatives potentiate anti-cancer effects in breast cancer cells. The aberrant expression of telomerase is critical to the continued proliferation of most cancer cells. Thus, telomerase is an attractive target for chemoprevention and treatment of breast cancer. 9cUAB30 is a novel synthetic retinoid X receptor-selective retinoic acid (RA) that effectively reduces the tumorigenic phenotype in mouse breast carcinoma with lower toxic effects than natural retinoid treatments. We have assessed 9cUAB30 retinoic acid treatment of human breast cancer cells to determine the potential of this drug as an effective telomerase inhibitor and its application to cancer therapy. 9cUAB30 was found to decrease DNA methyltransferase and telomerase expression in MDA-MB-361, T-47D, and MCF-7 human breast cancer cells and to inhibit the proliferation of these cells. This low-toxicity retinoid also reduced colony formation in soft agar assays in each of these cell types. Combination treatments of 9cUAB30 and all-trans RA proved to be synergistically more effective than either RA alone, further suggesting a possible general epigenetic mechanism that contributes to the anti-telomerase activity of the retinoids. Therefore, the novel retinoid, 9cUAB30, is effective in inhibiting the growth of human breast cancer cells, its anti-cancer effects appear to be related to telomerase inhibition and the mechanism for this process could be mediated through epigenetic modifications. PMID:17273765

Hansen, Nathan J; Wylie, Rebecca C; Phipps, Sharla M O; Love, William K; Andrews, Lucy G; Tollefsbol, Trygve O

2007-03-01

90

Kinetics of hyperpolarized 13C1-pyruvate transport and metabolism in living human breast cancer cells  

PubMed Central

Metabolic fluxes can serve as specific biomarkers for detecting malignant transformations, tumor progression, and response to microenvironmental changes and treatment procedures. We present noninvasive hyperpolarized 13C NMR investigations on the metabolic flux of pyruvate to lactate, in a well-controlled injection/perfusion system using T47D human breast cancer cells. Initial rates of pyruvate-to-lactate conversion were obtained by fitting the hyperpolarized 13C and ancillary 31P NMR data to a model, yielding both kinetic parameters and mechanistic insight into this conversion. Transport was found to be the rate-limiting process for the conversion of extracellular pyruvate to lactate with Km = 2.14 ± 0.03 mM, typical of the monocarboxylate transporter 1 (MCT1), and a Vmax = 27.6 ± 1.1 fmol·min?1·cell?1, in agreement with the high expression level of this transporter. Modulation of the environment to hypoxic conditions as well as suppression of cells' perfusion enhanced the rate of pyruvate-to-lactate conversion, presumably by up-regulation of the MCT1. Conversely, the addition of quercetin, a flavonoidal MCT1 inhibitor, markedly reduces the apparent rate of pyruvate-to-lactate conversion. These results suggest that hyperpolarized 13C1-pyruvate may be a useful magnetic resonance biomarker of MCT regulation and malignant transformations in breast cancer.

Harris, Talia; Eliyahu, Galit; Frydman, Lucio; Degani, Hadassa

2009-01-01

91

Alpha Cyano-4-Hydroxy-3-Methoxycinnamic Acid Inhibits Proliferation and Induces Apoptosis in Human Breast Cancer Cells  

PubMed Central

This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer.

Hamdan, Lamia; Arrar, Zoheir; Al Muataz, Yacoub; Suleiman, Lutfi; Negrier, Claude; Mulengi, Joseph Kajima; Boukerche, Habib

2013-01-01

92

Chemical and biological differentiation of three human breast cancer cell types using time-of-flight secondary ion mass spectrometry (TOF-SIMS)  

SciTech Connect

We use Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) to image and classify individual cells based on their characteristic mass spectra. Using statistical data reduction on the large data sets generated during TOF-SIMS analysis, similar biological materials can be differentiated based on a combination of small changes in protein expression, metabolic activity and cell structure. We apply this powerful technique to image and differentiate three carcinoma-derived human breast cancer cell lines (MCF-7, T47D and MDA-MB-231). In homogenized cells, we show the ability to differentiate the cell types as well as cellular compartments (cytosol, nuclear and membrane). These studies illustrate the capacity of TOF-SIMS to characterize individual cells by chemical composition, which could ultimately be applied to detect and identify single aberrant cells within a normal cell population. Ultimately, we anticipate characterizing rare chemical changes that may provide clues to single cell progression within carcinogenic and metastatic pathways.

Kulp, K S; Berman, E F; Knize, M G; Shattuck, D L; Nelson, E J; Wu, L; Montgomery, J L; Felton, J S; Wu, K J

2006-01-09

93

Role of metabolism in the effects of genistein and its phase II conjugates on the growth of human breast cell lines.  

PubMed

Genistein has been investigated for several decades for its potential role in breast cancer prevention. Previous researches have shown that glucuronide and sulfate conjugates are the major species circulating in the blood after genistein ingestion. It was hypothesized that enzymes (UDP-glucuronosyltransferases, sulphotransferases, ?-glucuronidases, and sulphatases) present in breast tissues would catalyze the inter-conversion between the aglycone and the conjugates in situ. Therefore, our aim was to investigate how genistein, genistein-7-glucuronide (G-7-G), genistein-7-sulfate (G-7-S), and 4'-sulfate (G-4'-S) were metabolized in mammary cells and to determine the effects of metabolism on their proliferative actions using cultured breast cell lines. As expected, genistein stimulated the cell growth of breast cancer cells (MCF-7 and T47D) concentration-dependently at lower concentrations but inhibited their growth at higher concentration. It showed low activities in a non-tumorigenic cell line (MCF-10A) due to the absence of ER?. Genistein was extensively metabolized to glucuronides by MCF-7 and to sulfates by T47D, while it was poorly metabolized by MCF-10A. G-7-G displayed weak stimulation activity in breast cancer cells. G-7-G underwent extensive metabolism in T47D and MCF-10A but not in MCF-7. The proliferative effects of G-7-G on MCF-7 and T47D were associated with its hydrolysis to genistein in these cells. In contrast, G-7-S and G-4'-S were not metabolized by these three cells and had no effects on their growth. In conclusion, production of phase II metabolites did not affect the proliferation effect of genistein on MCF-7 and T47D. Deconjugation was correlated to the apparent proliferative effects of G-7-G in breast cancer cells. PMID:22415614

Yuan, Bo; Wang, Linglan; Jin, Yi; Zhen, Huijuan; Xu, Pingwei; Xu, Youjun; Li, Chibing; Xu, Haiyan

2012-03-14

94

Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer.  

PubMed

Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. PMID:21464042

Cerliani, Juan P; Guillardoy, Tomás; Giulianelli, Sebastián; Vaque, José P; Gutkind, J Silvio; Vanzulli, Silvia I; Martins, Rubén; Zeitlin, Eduardo; Lamb, Caroline A; Lanari, Claudia

2011-04-04

95

Isothiocyanates Repress Estrogen Receptor ? Expression in Breast Cancer Cells  

PubMed Central

The isothiocyantes (ITCs) have long been known to possess chemopreventive activities for varieties of neoplasms including breast cancer, but the molecular mechanism by which ITCs prevent breast cancer development has not been established. In this study, we investigated the effects of benzyl and phenethyl isothiocyanate (BITC and PEITC) on the estrogen-stimulated growth of estrogen receptor alpha (ER?)-positive breast cancer MCF7 and T-47D cells. BITC and PEITC inhibited estrogen-stimulated cell growth and reduced the expression levels of ER? in MCF7 and T-47D cells in a dose and time -dependent and reversible manner. In addition, BITC and PEITC also abrogated the transcriptional activity of ER? and hence inhibited estrogen-stimulated expression of the estrogen responsive gene, pS2. These results demonstrated that BITC and PEITC function as potent ER? disruptors to abrogate mitogenic estrogen signaling in ER-positive breast cancer cells, which provides a molecular explanation for the growth inhibitory function of ITCs in breast cancer development, and a rational for further exploration of ITCs as chemopreventive agents for human mammary carcinogenesis.

Kang, Lianguo; Ding, Ling; Wang, Zhao-Yi

2008-01-01

96

Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and malignant human breast, and comparison with other normal tissues.  

PubMed Central

The expression of basic fibroblast growth factor (bFGF) and two of its receptors, FGFR1 and FGFR2, was detected using the polymerase chain reaction, and quantified by comparison to the relative amount of product obtained following co-amplification of the ubiquitous glyceraldehyde phosphate dehydrogenase transcript. Varying levels were found in the vast majority of both cancer and non-malignant breast biopsies as well as in samples of several other normal human tissues. Significantly less bFGF was present in cancers (P less than 0.0001). Similarly, FGFR2 product was also much less in cancer tissues (P = 0.0078), as was FGFR1 (P = 0.002). FGFR1 levels in cancers tended to be higher in those which were oestrogen receptor positive (P less than 0.06). Amplification of different coding regions showed evidence of variant forms of FGFR1 RNA. Cancers appeared to have a significantly greater proportion of PCR product corresponding to the region between the third immunoglobulin like domain and the tyrosine kinase domain (P = 0.046). Differential expression was observed in breast cell lines, with bFGF in the normal derived HBL100, HBR SV1.6.1 and 184A1 but little or none in ZR-75-1, MCF-7, T47D and MDA-MB-231. FGFR1 was present in most of these but FGFR2 was absent from T47D, MDA-MB-231 and HBL100. ZR-75-1 cells had a marked preponderance of FGFR1 variants lacking part of the coding sequence. Aberrant receptor processing may provide clues concerning the role of FGF's and their potential involvement in malignancy. Images Figure 3

Luqmani, Y. A.; Graham, M.; Coombes, R. C.

1992-01-01

97

KISS1R induces invasiveness of estrogen receptor-negative human mammary epithelial and breast cancer cells.  

PubMed

Kisspeptins (KPs), peptide products of the KISS1 metastasis-suppressor gene, are endogenous ligands for a G protein-coupled receptor (KISS1R). KISS1 acts as a metastasis suppressor in numerous human cancers. However, recent studies have demonstrated that an increase in KISS1 and KISS1R expression in patient breast tumors correlates with higher tumor grade and metastatic potential. We have shown that KP-10 stimulates invasion of estrogen receptor ? (ER?)-negative MDA-MB-231 breast cancer cells via transactivation of the epidermal growth factor receptor (EGFR). Here, we report that either KP-10 treatment of ER?-negative nonmalignant mammary epithelial MCF10A cells or expression of KISS1R in MCF10A cells induced a mesenchymal phenotype and stimulated invasiveness. Similarly, exogenous expression of KISS1R in ER?-negative SKBR3 breast cancer cells was sufficient to trigger invasion and induced extravasation in vivo. In contrast, KP-10 failed to transactivate EGFR or stimulate invasiveness in the ER?-positive MCF7 and T47D breast cancer cells. This suggested that ER? negatively regulates KISS1R-dependent breast cancer cell migration, invasion, and EGFR transactivation. In support of this, we found that these KP-10-induced effects were ablated upon exogenous expression of ER? in the MDA-MB-231 cells, by down-regulating KISS1R expression. Lastly, we have identified IQGAP1, an actin cytoskeletal binding protein as a novel binding partner of KISS1R, and have shown that KISS1R regulates EGFR transactivation in breast cancer cells in an IQGAP1-dependent manner. Overall, our data strongly suggest that the ER? status of mammary cells dictates whether KISS1R may be a novel clinical target for treating breast cancer metastasis. PMID:23525242

Cvetkovic, Donna; Dragan, Magdalena; Leith, Sean J; Mir, Zuhaib M; Leong, Hon S; Pampillo, Macarena; Lewis, John D; Babwah, Andy V; Bhattacharya, Moshmi

2013-03-24

98

Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells  

PubMed Central

Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra essential oil hydrodistilled at 100 oC was more potent than the essential oil prepared at 78 oC in inducing cancer cell death, preventing the cellular network formation (MDA-MB-231) cells on Matrigel, causing the breakdown of multicellular tumor spheroids (T47D cells), and regulating molecules involved in apoptosis, signal transduction, and cell cycle progression. Conclusions Similar to our previous observations in human bladder cancer cells, Boswellia sacra essential oil induces breast cancer cell-specific cytotoxicity. Suppression of cellular network formation and disruption of spheroid development of breast cancer cells by Boswellia sacra essential oil suggest that the essential oil may be effective for advanced breast cancer. Consistently, the essential oil represses signaling pathways and cell cycle regulators that have been proposed as therapeutic targets for breast cancer. Future pre-clinical and clinical studies are urgently needed to evaluate the safety and efficacy of Boswellia sacra essential oil as a therapeutic agent for treating breast cancer.

2011-01-01

99

Canola oil inhibits breast cancer cell growth in cultures and in vivo and acts synergistically with chemotherapeutic drugs.  

PubMed

Certain fatty acids in canola oil (CAN) have been associated with a reduced risk of breast cancer. This study assessed the effects of CAN on proliferation and death of human breast cancer cells in vitro and in vivo in chemically induced mammary carcinogenesis. We hypothesize that CAN reduces breast cancer cell growth by inducing cell death. In a series of in vitro experiments, human breast cancer T47D and MCF-7 cells were cultured and treated with CAN and two chemotherapeutic drugs, tamoxifen and cerulenin. Cell proliferation and caspase-3 and p53 activities were measured. Reduced cancer cell growth and increased expression of caspase-3 and p53 were seen in T47D and MCF-7 cells treated with CAN. Moreover, CAN showed synergistic cancer cell growth inhibition effects with tamoxifen and cerulenin. In a subsequent live animal experiment, 42 female Sprague-Dawley rats were randomly assigned to corn oil (CORN) or CAN diets, and mammary tumors were chemically induced by N-nitroso-N-methylurea. CAN-dieted rats had reduced tumor volumes and showed an increased survival rate as compared to CORN-dieted rats. We demonstrated that CAN has suppressive effects on cancer growth, and reduces tumor volumes. The results suggest that CAN may have inhibitory effects on breast cancer cell growth, and warrants further investigation of the synergistic effects of CAN with anti-cancer drugs. PMID:20730604

Cho, Kyongshin; Mabasa, Lawrence; Fowler, Andrea W; Walsh, Dana M; Park, Chung S

2010-08-22

100

Prodigiosin down-regulates survivin to facilitate paclitaxel sensitization in human breast carcinoma cell lines.  

PubMed

Prodigiosin is a bacterial metabolite with potent anticancer activity, which is attributed to its proapoptotic effect selectively active in malignant cells. Still, the molecular mechanisms whereby prodigiosin induces apoptosis remain largely unknown. In particular, the role of survivin, a vital inhibitor of apoptosis, in prodigiosin-induced apoptosis has never been addressed before and hence was the primary goal of this study. Our results showed that prodigiosin dose-dependently induced down-regulation of survivin in multiple breast carcinoma cell lines, including MCF-7, T-47D and MDA-MB-231. This down-regulation is mainly regulated at the level of transcription, as prodigiosin reduced the levels of both survivin mRNA and survivin promoter activity but failed to rescue survivin expression when proteasome-mediated degradation is abolished. Importantly, overexpression of survivin rendered cells more resistant to prodigiosin, indicating an essential role of survivin down-regulation in prodigiosin-induced apoptosis. In addition, we found that prodigiosin synergistically enhanced cell death induced by paclitaxel, a chemotherapy drug known to up-regulate survivin that in turn confers its own resistance. This paclitaxel sensitization effect of prodigiosin is ascribed to the lowering of survivin expression, because prodigiosin was shown to counteract survivin induction by paclitaxel and, notably, the sensitization effect was severely abrogated in cells that overexpress survivin. Taken together, our results argue that down-regulation of survivin is an integral component mediating prodigiosin-induced apoptosis in human breast cancer cells, and further suggest the potential of prodigiosin to sensitize anticancer drugs, including paclitaxel, in the treatment of breast cancer. PMID:19133282

Ho, Tsing-Fen; Peng, Yu-Ta; Chuang, Show-Mei; Lin, Shin-Chang; Feng, Bo-Lin; Lu, Chien-Hsing; Yu, Wan-Ju; Chang, Jo-Shu; Chang, Chia-Che

2008-12-24

101

Real-Time Growth Kinetics Measuring Hormone Mimicry for ToxCast Chemicals in T-47D Human Ductal Carcinoma Cells  

EPA Science Inventory

High-throughput screening (HTS) assays capable of profiling thousands of environmentally relevant chemicals for in vitro biological activity provide useful information on the potential for disrupting endocrine pathways. Disruption of the estrogen signaling pathway has been implic...

102

Immunotherapeutic Potential of Anti-Human Endogenous Retrovirus-K Envelope Protein Antibodies in Targeting Breast Tumors  

PubMed Central

Background The envelope (env) protein of the human endogenous retrovirus type K (HERV-K) family is commonly expressed on the surface of breast cancer cells. We assessed whether HERV-K env is a potential target for antibody-based immunotherapy of breast cancer. Methods We examined the expression of HERV-K env protein in various malignant (MDA-MB-231, MCF-7, SKBR3, MDA-MB-453, T47D, and ZR-75-1) and nonmalignant (MCF-10A and MCF-10AT) human breast cell lines by immunoblot, enzyme-linked immunosorbent assay, immunofluorescence staining, and flow cytometry. Anti-HERV-K env monoclonal antibodies (mAbs; 6H5, 4D1, 4E11, 6E11, and 4E6) were used to target expression of HERV-K, and antitumor effects were assessed by quantifying growth and apoptosis of breast cancer cells in vitro, and tumor growth in vivo in mice (n = 5 per group) bearing xenograft tumors. The mechanisms responsible for 6H5 mAb–mediated effects were investigated by microarray assays, flow cytometry, immunoblot, and immunofluorescence staining. The expression of HERV-K env protein was assessed in primary breast tumors (n = 223) by immunohistochemistry. All statistical tests were two-sided. Results The expression of HERV-K env protein in malignant breast cancer cell lines was substantially higher than nonmalignant breast cells. Anti–HERV-K-specific mAbs inhibited growth and induced apoptosis of breast cancer cells in vitro. Mice treated with 6H5 mAb showed statistically significantly reduced growth of xenograft tumors compared with mice treated with control immunoglobulin (control [mIgG] vs 6H5 mAb, for tumors originating from MDA-MB-231 cells, mean size = 1448.33 vs 475.44 mm3; difference = 972.89 mm3, 95% CI = 470.17 to 1475.61 mm3; P < .001). Several proteins involved in the apoptotic signaling pathways were overexpressed in vitro in 6H5 mAb–treated malignant breast cells compared with mIgG-treated control. HERV-K expression was detected in 148 (66%) of 223 primary breast tumors, and a higher rate of lymph node metastasis was associated with HERV-K-positive compared with HERV-K-negative tumors (43% vs 23%, P = .003). Conclusion Monoclonal antibodies against HERV-K env protein show potential as novel immunotherapeutic agents for breast cancer therapy.

Rycaj, Kiera; Plummer, Joshua B.; Li, Ming; Yin, Bingnan; Frerich, Katherine; Garza, Jeremy G.; Shen, Jianjun; Lin, Kevin; Yan, Peisha; Glynn, Sharon A.; Dorsey, Tiffany H.; Hunt, Kelly K.; Ambs, Stefan; Johanning, Gary L.

2012-01-01

103

Immunologic analysis of human breast cancer progesterone receptors. 2. Structure, phosphorylation, and processing  

SciTech Connect

The authors have used a monoclonal antibody (MAb) directed against chick oviduct progesterone receptors (PR), that cross-reacts with human PR, to analyze PR structure and phosphorylation. This MAb, designated PR-6, interacts only with B receptors (M/sub r/ 120,000) of T47D human breast cancer cells; it has no affinity for A receptors (M/sub r/ 94,000) or for proteolytic fragments from either protein. The antibody immunoprecipitates native B receptors and was used to study the structure of native untransformed 8S and transformed 4S receptors, using sucrose density gradient analysis, photoaffinity labeling, and gel electrophoresis. The independence of A- and B-receptor complexes was confirmed by the fining that purified, transformed B receptors bind well to DNA-cellulose. Additional studies focused on the covalent modifications of receptors. The previously described shifts in apparent molecular weight of nuclear PR following R5020 treatment using in situ photoaffinity labeling. To show whether these shifts can be explained by receptor phosphorylation, untreated cells and hormone-treated cells were metabolically labeled with (/sup 32/P)orthophosphate, and the B receptors were isolated by immunoprecipitation with PR-6 and analyzed by sodium dodecyl sulfate (SDS) gel electrophoresis. In both treatment states, B receptors were labeled in vivo with /sup 32/P, thus demonstrating directly that human PR are phosphoproteins. Since B receptors were labeled in the absence of hormone and also after their in vivo transformation by hormone, they appear to be substrates for two phosphorylation reactions, one in the untransformed state and another after they are tightly bound to chromatin. The second phosphorylation may account for the mobility shift of the receptors on SDS gels. On the basis of these data a model of human PR structure and subcellular receptor dynamics is presented.

Wei, L.L.; Sheridan, P.L.; Krett, N.L.; Francis, M.D.; Toft, D.O.; Edwards, D.P.; Horwitz, K.B.

1987-09-22

104

Modeling mixtures of environmental estrogens found in U.S. surface waters with an in vitro estrogen mediated transcriptionai activation assay (T47D-KBluc).  

EPA Science Inventory

There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. Environmental estrogens can come from various sources including concentrated animal feedlot operations (CAFO), municipa...

105

Tyrosyl phosphorylated PAK1 regulates breast cancer cell motility in response to prolactin through filamin A.  

PubMed

The p21-activated serine-threonine kinase (PAK1) is activated by small GTPase-dependent and -independent mechanisms and regulates cell motility. Both PAK1 and the hormone prolactin (PRL) have been implicated in breast cancer by numerous studies. We have previously shown that the PRL-activated tyrosine kinase JAK2 (Janus tyrosine kinase 2) phosphorylates PAK1 in vivo and identified tyrosines (Tyr) 153, 201, and 285 in the PAK1 molecule as sites of JAK2 tyrosyl phosphorylation. Here, we have used human breast cancer T47D cells stably overexpressing PAK1 wild type or PAK1 Y3F mutant in which Tyr(s) 153, 201, and 285 were mutated to phenylalanines to demonstrate that phosphorylation of these three tyrosines are required for maximal PRL-dependent ruffling. In addition, phosphorylation of these three tyrosines is required for increased migration of T47D cells in response to PRL as assessed by two independent motility assays. Finally, we show that PAK1 phosphorylates serine (Ser) 2152 of the actin-binding protein filamin A to a greater extent when PAK1 is tyrosyl phosphorylated by JAK2. Down-regulation of PAK1 or filamin A abolishes the effect of PRL on cell migration. Thus, our data presented here bring some insight into the mechanism of PRL-stimulated motility of breast cancer cells. PMID:23340249

Hammer, Alan; Rider, Leah; Oladimeji, Peter; Cook, Leslie; Li, Quanwen; Mattingly, Raymond R; Diakonova, Maria

2013-01-22

106

Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells  

PubMed Central

Whereas estrogen–estrogen receptor ? (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)–negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER–mediated growth of breast cancer cells and could, thus, be a potential therapeutic target.

Su, Dan; Fu, Xiaoying; Fan, Songqing; Wu, Xiao; Wang, Xin-Xin; Fu, Liya; Dong, Xue-Yuan; Ni, Jianping Jenny; Fu, Li; Zhu, Zhengmao; Dong, Jin-Tang

2012-01-01

107

Early estrogen-induced metabolic changes and their inhibition by actinomycin D and cycloheximide in human breast cancer cells: sup 31 P and sup 13 C NMR studies  

SciTech Connect

Metabolic changes following estrogen stimulation and the inhibition of these changes in the presence of actinomycin D and cycloheximide were monitored continuously in perfused human breast cancer T47D clone 11 cells with {sup 31}P and {sup 13}C NMR techniques. The experiments were performed by estrogen rescue of tamoxifen-treated cells. Immediately after perfusion with estrogen-containing medium, a continuous enhancement in the rates of glucose consumption, lactate production by glycolysis, and glutamate synthesis by the Krebs cycle occurred with a persistent 2-fold increase at 4 hr. Pretreatment with either actinomycin D or cycloheximide, at concentrations known to inhibit mRNA and protein synthesis, respectively, and simultaneous treatment with estrogen and each inhibitor prevented the estrogen-induced changes in glucose metabolism. This suggested that the observed estrogen stimulation required synthesis of mRNA and protein. These inhibitors also modulated several metabolic activities that were not related to estrogen stimulation. The observed changes in the in vivo kinetics of glucose metabolism may provide a means for the early detection of the response of human breast cancer cells to estrogen versus tamoxifen treatment.

Neeman, M.; Degani, H. (Weizmann Institute of Science, Rehovot (Israel))

1989-07-01

108

N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth  

PubMed Central

Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA) on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa) MCF-7 and T47D cells. 17 ?-estradiol (E2) enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM) treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2). E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0) as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear) estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ER? agonist failed to elicit, and ER? knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1) may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.

Cao, WenQing; Ma, ZhiFan; Rasenick, Mark M.; Yeh, ShuYan; Yu, JiangZhou

2012-01-01

109

Stable Transfection and Overexpression of Metallothionein Isoform 3 Inhibits the Growth of MCF7 and Hs578T Cells but not that of T-47D or MDA-MB-231 Cells  

Microsoft Academic Search

The third isoform of metallothionein (MT-3) is overexpressed in some breast cancers and its expression is associated with a poor disease outcome. In the PC-3 prostate cancer cell line, MT-3 expression has been shown to inhibit cell growth and increase drug resistance. The goal of the present study was to determine if MT-3 overexpression would influence the growth of human

Volkan Gurel; Donald A. Sens; Seema Somji; Scott H. Garrett; Joginder Nath; Mary Ann Sens

2003-01-01

110

PTP1B Suppresses Prolactin Activation of Stat5 in Breast Cancer Cells  

PubMed Central

Basal levels of nuclear localized, tyrosine phosphorylated Stat5 are present in healthy human breast epithelia. In contrast, Stat5 phosphorylation is frequently lost during breast cancer progression, a finding that correlates with loss of histological differentiation and poor patient prognosis. Identifying the mechanisms underlying loss of Stat5 phosphorylation could provide novel targets for breast cancer therapy. Pervanadate, a general tyrosine phosphatase inhibitor, revealed marked phosphatase regulation of Stat5 activity in breast cancer cells. Lentiviral-mediated shRNA allowed specific examination of the regulatory role of five tyrosine phosphatases (PTP1B, TC-PTP, SHP1, SHP2, and VHR), previously implicated in Stat5 regulation in various systems. Enhanced and sustained prolactin-induced Stat5 tyrosine phosphorylation was observed in T47D and MCF7 breast cancer cells selectively in response to PTP1B depletion. Conversely, PTP1B overexpression suppressed prolactin-induced Stat5 tyrosine phosphorylation. Furthermore, PTP1B knockdown increased Stat5 reporter gene activity. Mechanistically, PTP1B suppression of Stat5 phosphorylation was mediated, at least in part, through inhibitory dephosphorylation of the Stat5 tyrosine kinase, Jak2. PTP1B knockdown enhanced sensitivity of T47D cells to prolactin phosphorylation of Stat5 by reducing the EC50 from 7.2 nmol/L to 2.5 nmol/L. Immunohistochemical analyses of two independent clinical breast cancer materials revealed significant negative correlations between levels of active Stat5 and PTP1B, but not TC-PTP. Collectively, our data implicate PTP1B as an important negative regulator of Stat5 phosphorylation in invasive breast cancer.

Johnson, Kevin J.; Peck, Amy R.; Liu, Chengbao; Tran, Thai H.; Utama, Fransiscus E.; Sjolund, Ashley B.; Schaber, John D.; Witkiewicz, Agnieszka K.; Rui, Hallgeir

2010-01-01

111

Antiproliferative activity of L-asparaginase of Tetrahymena pyriformis on human breast cancer cell lines.  

PubMed

Purified L-asparaginase of Tetrahymena pyriformis is a multi-subunit enzyme exhibiting protein kinase activity as well. The enzyme's L-asparaginase activity is affected by its phosphorylation state. Both native and dephosphorylated L-asparaginase show antiproliferative activity on three breast cancer cell lines (T47D, BT20 and MCF-7) and on Walker 256 cells. These cells do not possess measurable L-asparaginase or L-asparagine synthetase activity. When T47D cells are treated for different times with L-asparaginase and then placed in fresh medium, the growth of cells treated for 1, 3, or 6 hours is initiated and parallels control curve, while the growth of cells treated for 24 or 48 hours with L-asparaginase stays at the same inhibitory level (24 h treatment) or continues to drop (48 h treatment). Addition of D-asparagine, a competitive inhibitor of T. pyriformis L-asparaginase, counteracts the antiproliferative activity of L-asparaginase, indicating that L-asparaginase and not the kinase activity is responsible for that effect. PMID:2125695

Kyriakidis, D A; Tsirka, S A; Tsavdaridis, I K; Iliadis, S N; Kortsaris, A H

1990-08-10

112

Autocrine human GH promotes radioresistance in mammary and endometrial carcinoma cells.  

PubMed

Although recent advances in breast cancer treatment regimes have improved patient prognosis, resistance to breast cancer therapies, such as radiotherapy, is still a major clinical challenge. In the current study, we have investigated the role of autocrine human GH (hGH) in resistance to ionising radiation (IR)-based therapy. Cell viability and total cell number assays demonstrated that autocrine hGH promoted cell regrowth in the mammary carcinoma cell lines, MDA-MB-435S and T47D, and the endometrial carcinoma cell line, RL95-2, following treatment with IR. In addition, autocrine hGH enhanced MDA-MB-435S and T47D cell clonogenic survival following radiation exposure. The enhanced clonogenic survival afforded by autocrine hGH was mediated by JAK2 and Src kinases. Investigation into the DNA repair capacity demonstrated that autocrine hGH reduced IR-induced DNA damage in MDA-MB-435S and T47D cells. Functional antagonism of hGH increased RL95-2 sensitivity to IR in cell viability and total cell number assays, reduced clonogenic survival and enhanced the induction of DNA damage. Thus, autocrine hGH reduced sensitivity to treatment with IR in mammary and endometrial carcinoma cell lines in vitro, while functional antagonism of hGH sensitised endometrial carcinoma cells to IR. Functional antagonism of hGH, used in conjunction with radiotherapy, may therefore enhance treatment efficacy and improve the prognosis of patients with breast and endometrial cancer. PMID:22807498

Bougen, Nicola M; Steiner, Michael; Pertziger, Mikhail; Banerjee, Arindam; Brunet-Dunand, Severine E; Zhu, Tao; Lobie, Peter E; Perry, Jo K

2012-09-14

113

Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines.  

PubMed

There is a lack of understanding of the casual mechanisms behind the observation that some breast adenocarcinomas have identical morphology and comparatively different cellular growth behavior. This is exemplified by a differential response to radiation, chemotherapy, and other biological intervention therapies. Elevated concentrations of the free radical nitric oxide (NO), coupled with the up-regulated enzyme nitric oxide synthase (NOS) which produces NO, are activities which impact tumor growth. Previously, we adapted four human breast cancer cell lines: BT-20, Hs578T, T-47D, and MCF-7 to elevated concentrations of nitric oxide (or high NO [HNO]). This was accomplished by exposing the cell lines to increasing levels of an NO donor over time. Significantly, the HNO cell lines grew faster than did each respective ("PARENT") cell line even in the absence of NO donor-supplemented media. This was evident despite each "parent" being morphologically equivalent to the HNO adapted cell line. Herein, we characterize the HNO cells and their biological attributes against those of the parent cells. Pairs of HNO/parent cell lines were then analyzed using a number of key cellular activity criteria including: cell cycle distribution, DNA ploidy, response to DNA damage, UV radiation response, X-ray radiation response, and the expression of significant cellular enzymes. Other key enzyme activities studied were NOS, p53, and glutathione S-transferase-pi (GST-pi) expression. HNO cells were typified by a far more aggressive pattern of growth and resistance to various treatments than the corresponding parent cells. This was evidenced by a higher S-phase percentage, variable radioresistance, and up-regulated GST-pi and p53. Taken collectively, this data provides evidence that cancer cells subjected to HNO concentrations become resistant to free radicals such as NO via up-regulated cellular defense mechanisms, including p53 and GST-pi. The adaptation to NO may explain how tumor cells acquire a more aggressive tumor phenotype. PMID:23238815

Vesper, B J; Onul, A; Haines, G K; Tarjan, G; Xue, J; Elseth, K M; Aydogan, B; Altman, M B; Roeske, J C; Paradise, W A; De Vitto, H; Radosevich, J A

2012-12-14

114

Regulation of 1,25-dihydroxyvitamin D, receptors by (/sup 3/H)-1,25-dihydroxyvitamin D/sub 3/ in cultured cells (T-47D): evidence for receptor upregulation  

SciTech Connect

The authors examined the effect of 1,25-(OH)/sub 2/D/sub 3/ on receptor concentration in cultured cells (T-47D). Two days prior to experiment, cells were fed with RPMI 1640 + 10% serum and 24-32 hours prior to experiment the media was replaced with RPMI 1640 + 25 mM Hepes + 1% serum. (/sup 3/H)-1,25-(OH)/sub 2/D/sub 3/ +/- 100-fold molar excess cold hormone was used to treat the cells. Occupied receptors were measured in freshly prepared cytosols. Total receptors were measured following a 16-hour incubation of cytosols in the presence of 0.6 nM (/sup 3/H)-1,25-(OH)/sub 2/D/sub 3/ +/- 100-fold molar excess of cold hormone at 4/sup 0/C. Treatment of cell cultures for 16-18 hours with 0.5-1.0 nM (/sup 3/H)-1,25-(OH)/sub 2/D/sub 3/ resulted in a 30-40% receptor occupancy by the hormone and a 2- to 3-fold increase in total cell receptor as compared to vehicle-treated controls. Time course studies showed a rapid increase in total receptors up to 16 hours post-treatment in the face of declining receptor occupancy. Actinomycin D blocked the (/sup 3/H)-1,25-(OH)/sub 2/D/sub 3/-dependent rise in cell receptor. The physiological significance of this receptor upregulation is not known nor is it known whether upregulation results from synthesis of new receptors and/or is the result of the activation of preformed receptors by a inducible activator protein.

Reinhardt, T.A.; Horst, R.L.

1986-03-01

115

Radiation resistance due to high expression of miR-21 and G2/M checkpoint arrest in breast cancer cells  

PubMed Central

Background There is evidence that the extent of the G2/M arrest following irradiation is correlated with tumour cell survival and hence therapeutic success. We studied the regulation of cellular response to radiation treatment by miR-21-mediated modulation of cell cycle progression in breast cancer cells and analysed miR-21 expression in breast cancer tissue samples with long-term follow up. Methods The miR-21 expression levels were quantified (qRT-PCR) in a panel of 86 cases of invasive breast carcinomas in relation to metastasis free survival. The cellular radiosensitivity of human breast cancer cells after irradiation was determined comparing two cell lines (T47D and MDA-MB-361) by cell proliferation and colony forming assays. The influence of miR-21 overexpression or downregulation on cell cycle progression and G2/M checkpoint arrest after irradiation was assessed by flow cytometric analysis. Results The expression of miR-21 was transiently increased 8 hours after irradiation in the radioresistant T47D cells and significantly changed with lower extent in radiosensitive MDA-MB-361 cells. Anti-miR-21 treated breast cancer cells failed to exhibit the DNA damage-G2 checkpoint increase after irradiation. Apoptotic activity was significantly enhanced from 7% to 27% in T47D cells and from 18% to 30% in MDA-MB-361 cells 24 hours after 5 Gy irradiation. Additionally, we characterized expression of miR-21 in invasive breast carcinomas. In comparison to non-cancerous adjacent breast tissue, tumours samples had increased miR-21 expression that inversely correlated with the distant metastases-free survival of patients (p = 0.029). Conclusions Our data indicate that miR-21 expression in breast cancer cells contributes to radiation resistance by compromising cell cycle progression. These data point to the potential of combining radiotherapy with an anti-miR-21 as a potent G2/M check point inhibitor in overcoming radiation resistance of tumours.

2012-01-01

116

NTAKalpha and beta isoforms stimulate breast tumor cell growth by means of different receptor combinations.  

PubMed

Neural- and thymus-derived activator for ErbB kinases (NTAK) is a recently described member of the neuregulin family that binds directly to ErbB3 and ErbB4 and transactivates ErbB2. Rat NTAK has at least five alternative-spliced isoforms: alpha1, alpha2a, alpha2b, beta, and gamma. In order to understand their biological properties, this study focused on the NTAK alpha2a and beta isoforms, which have different EGF-like domains. The effect of these isoforms on cell growth and tyrosine phosphorylation in human breast cancer cells, MDA-MB-453 and T47D, was examined using the recombinant proteins. In terms of cell growth, NTAKalpha2a and NTAKbeta preferentially stimulate T47D cells and MDA-MB-453 cells, respectively, in a dose-dependent manner. Although both NTAKs induce the highest level of tyrosine phosphorylation of ErbB2, NTAKalpha2a and NTAKbeta preferentially induce ErbB3 and ErbB4 phosphorylation, respectively. Thus, NTAKalpha2a and NTAKbeta stimulate cell growth in different ways, by means of different combinations of receptors. PMID:10788804

Nakano, N; Higashiyama, S; Kajihara, K; Endo, T; Ishiguro, H; Yamada, K; Nagatsu, T; Taniguchi, N

2000-05-01

117

Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines  

PubMed Central

Background The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. Methods For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAMhigh breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAMlow breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. Results In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAMhigh cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAMlow cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. Conclusions The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer.

2012-01-01

118

Bisphenol-A-induced inactivation of the p53 axis underlying deregulation of proliferation kinetics, and cell death in non-malignant human breast epithelial cells.  

PubMed

Widespread distribution of bisphenol-A (BPA) complicates epidemiological studies of possible carcinogenic effects on the breast because there are few unexposed controls. To address this challenge, we previously developed non-cancerous human high-risk donor breast epithelial cell (HRBEC) cultures, wherein BPA exposure could be controlled experimentally. BPA consistently induced activation of the mammalian target of rapamycin (mTOR) pathway--accompanied by dose-dependent evasion of apoptosis and increased proliferation--in HRBECs from multiple donors. Here, we demonstrate key molecular changes underlying BPA-induced cellular reprogramming. In 3/3 BPA-exposed HRBEC cell lines, and in T47D breast cancer cells, proapoptotic negative regulators of the cell cycle (p53, p21(WAF1) and BAX) were markedly reduced, with concomitant increases in proliferation-initiating gene products (proliferating cell nuclear antigen, cyclins, CDKs and phosphorylated pRb). However, simultaneous exposure to BPA and the polyphenol, curcumin, partially or fully reduced the spectrum of effects associated with BPA alone, including mTOR pathway proteins (AKT1, RPS6, pRPS6 and 4EBP1). BPA exposure induced an increase in the ER? (Estrogen Receptor): ER? ratio--an effect also reversed by curcumin (analysis of variance, P < 0.02 for all test proteins). At the functional level, concurrent curcumin exposure reduced BPA-induced apoptosis evasion and rapid growth kinetics in all cell lines to varying degrees. Moreover, BPA extended the proliferation potential of 6/6 primary finite-life HRBEC cultures--another effect reduced by curcumin. Even after removal of BPA, 1/6 samples maintained continuous growth--a hallmark of cancer. We show that BPA exposure induces aberrant expression of multiple checkpoints that regulate cell survival, proliferation and apoptosis and that such changes can be effectively ameliorated. PMID:23222814

Dairkee, Shanaz H; Luciani-Torres, M Gloria; Moore, Dan H; Goodson, William H

2012-12-07

119

Enhanced translational efficiency of a novel transforming growth factor beta 3 mRNA in human breast cancer cells.  

PubMed Central

The mRNA for transforming growth factor beta 3 (TGF-beta 3) includes a long (1.1-kb) 5' noncoding region which exerts a potent inhibitory effect on translational efficiency. We now report that many human breast cancer cell lines (T47-D, SK-BR-3, ZR-75-1, and BT-474) express two mRNA species for TGF-beta 3: the 3.5-kb transcript previously described as the only TGF-beta 3 mRNA species in cells and a novel 2.6-kb transcript which lacks approximately 870 nucleotides from the 5' noncoding region. The 5' end of the shorter transcript was sequenced, establishing it to be a 5' truncation of the full-length TGF-beta 3 transcript. Estradiol decreased mRNA levels of both TGF-beta 3 mRNA transcripts to an equivalent degree in estrogen receptor-positive cells. In contrast, the synthetic progestin gestodene altered the relative abundance of the two transcripts, preferentially diminishing the expression of the 2.6-kb transcript. The potential for enhanced mRNA translation attributable to the shorter 5' noncoding region was evaluated by transfection of cells with chimeric plasmid constructs in which the transcription unit consisted of coding sequence for chloramphenicol acetyltransferase downstream of the 5' noncoding sequence from TGF-beta 3. The translational efficiency of chloramphenicol acetyltransferase-encoding mRNA containing the shorter 5' noncoding region of the 2.6-kb TGF-beta 3 transcript was approximately seven times greater than with the full-length 5' noncoding region of TGF-beta 3. Polysome analysis of TGF-beta 3 mRNA in SK-BR-3 cells supported the hypothesis that the 2.6-kb transcript was more actively engaged in translation. Images

Arrick, B A; Grendell, R L; Griffin, L A

1994-01-01

120

Lin28 Mediates Paclitaxel Resistance by Modulating p21, Rb and Let-7a miRNA in Breast Cancer Cells  

PubMed Central

Resistance to chemotherapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to tumor relapse after chemotherapy; however, the relationship between Lin28 and chemoresistance remained unknown. In this study, we investigated the association of Lin28 with paclitaxel resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines and tumor tissues. We found that the expression level of Lin28 was closely associated with the resistance to paclitaxel treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to paclitaxel than the MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which had low-level expression of Lin28. Knocking down of Lin28 in Lin28 high expression T47D cells increased the sensitivity to paclitaxel treatment, while stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to paclitaxel treatment, resulting in a significant increase of IC50 values of paclitaxel. Transfection with Lin28 also significantly inhibited paclitaxel-induced apoptosis. We also found that Lin28 expression was dramatically increased in tumor tissues after neoadjuvant chemotherapy or in local relapse or metastatic breast cancer tissues. Moreover, further studies showed that p21, Rb and Let-7 miRNA were the molecular targets of Lin28. Overexpression of Lin28 in breast cancer cells considerably induced p21 and Rb expression and inhibited Let-7 miRNA levels. Our results indicate that Lin28 expression might be one mechanism underlying paclitaxel resistance in breast cancer, and Lin28 could be a potential target for overcoming paclitaxel resistance in breast cancer.

Lv, Kezhen; Liu, Liqun; Wang, Linbo; Yu, Jiren; Liu, Xiaojiao; Cheng, Yongxia; Dong, Minjun; Teng, Rongyue; Wu, Linjiao; Fu, Peifen; Deng, Wuguo; Hu, Wenxian; Teng, Lisong

2012-01-01

121

Therapeutic Implications of Progesterone Receptor-Mediated Regulation of Cell Cycle in Breast Cancer.  

National Technical Information Service (NTIS)

Since the 2007 summary report, we have made significant progress in elucidating the novel mechanisms by which PR regulates expression of E2F1, a key regulator of cell cycle progression, in T47D breast cancer cells. In addition to a direct regulatory pathw...

H. Wade

2008-01-01

122

A new in vitro bioassay for human calcitonin: validation and comparison to the rat hypocalcemia bioassay.  

PubMed

The human breast cancer cell line T 47 D expresses calcitonin (CT) receptors that are coupled to adenylate cyclase and which reveal a dose-dependent cyclic AMP response to CT. We used this model to establish an in vitro bioassay for synthetic human CT (hCT) preparations to overcome some of the obstacles of the standard rat hypocalcemia in vivo bioassay. The detection limit of the in vitro bioassay was 1 x 10(-10) M hCT (EC 50: 8.7 pM +/- 26%) compared to 7.3 x 10(-9) M (EC 50: 7.2 microM +/- 32%) for the in vivo bioassay. The relative potencies of test preparations revealed a good correlation (r = 0.89) and several hCT-related substances produced comparable results when tested by the two methods. The standard deviations of precision and accuracy, however, were significantly smaller (P less than 0.05) for the in vitro bioassay. According to these data the T 47 D in vitro bioassay is more sensitive, superior in precision and accuracy, and comparable in specificity to the rat hypocalcemia bioassay. PMID:1316197

Grauer, A; Raue, F; Reinel, H H; Schneider, H G; Schroth, J; Kabay, A; Brügger, P; Ziegler, R

1992-04-01

123

Hormones of pregnancy, alpha-feto protein, and reduction of breast cancer risk.  

PubMed

Parity profoundly reduces breast cancer (BC) risk later in life. It has been reasoned that hormones (either estradiol E2 or estriol E3), progesterone (P) or human chorionic gonadotropin (hCG) in the serum of pregnant women might lead to that reduction in risk. These agents have been shown to reduce BC incidence in nonpregnant rats. We investigated the hypothesis that exogenously added E2, E3, P, or hCG are not the proximal effectors of risk reduction, but that they elicit alpha-fetoprotein (alphaFP) from the nonpregnant liver, and that cFP is the proximal agent by which reduction of BC risk is obtained. Methylnitrosourea (MNU)-exposed animals were treated with saline, E3, E2 + P, E3 + P, hCG, or were allowed to experience pregnancy, and AFP levels were measured in the serum and subsequent tumor incidence was recorded. Human HepG2 liver cells in culture were treated with E3, E2 + P, P, or hCG and elicited AFP was measured in the media. The HepG2 culture media containing elicited AFP was assessed for its ability to inhibit proliferation of T47D cells when applied to these human BC cells in culture, and to inhibit the estrogen-induced phosphorylation of the estrogen receptor in T47D cells. For each condition in the prevention studies, hormone treatment reduced the incidence of BC to an extent similar to that reported by the original studies. In each condition, alphaFP levels in serum were elevated over that in control animals. In culture, treatment of human liver cells with E3, E2 + P, or hCG, but not P alone, led to increased levels of AFP in the media. Media containing hCG-elicited AFP inhibited the estrogen-stimulated proliferation of T47D cells in culture, and inhibited phosphorylation of the estrogen receptor, whereas, estrogens and hCG did not inhibit the growth of these tumor cells in culture. In conclusion, since the hormones of pregnancy elicit alphaFP from the liver, and alphaFP but not the hormones of pregnancy has direct antitumor properties, it is concluded that alphaFP is the proximal agent through which reduction in BC incidence is realized from the experience of pregnancy. PMID:18497072

Jacobson, Herbert I; Lemanski, Nicole; Narendran, Amithi; Agarwal, Anu; Bennett, James A; Andersen, Thomas T

2008-01-01

124

Breast asymmetry, sexual selection, and human reproductive success  

Microsoft Academic Search

Breasts of human females are large compared to those of closely related primate species, and they can thus be hypothesized recently or currently to have been subject to directional sexual selection. Here we show that (1) large breasts have higher levels of fluctuating asymmetry than small breasts, (2) breast fluctuating asymmetry is higher in women without children than in women

Randy Thornhill; M SOLER

1995-01-01

125

3-Methylcholanthrene Induces Differential Recruitment of Aryl Hydrocarbon Receptor to Human Promoters  

PubMed Central

The paper by Pansoy and coworkers investigates the effects of the aryl hydrocarbon receptor (AHR) ligand 3-methylcholanthrene (3MC) on recruitment of the AHR complex to human promoters in T47D breast cancer cells. The results are particularly important because they can be compared with a prior study using the potent AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the same cell line. The chromatin immunoprecipitation and promoter-focused microarrays (ChIP-chip) demonstrated that after treatment of T47D cells with 1?M 3MC, there were 241 AHR-3MC bound regions and many of these contained AHR-responsive elements. However, they also observed interactions with regions that do not contain these responsive elements, and subsequent analysis of selected target genes show that 3MC-dependent AHR binding did not necessarily predict Ah-responsiveness because induction, repression, and no effects were observed. A prior study with TCDD demonstrated that both 3MC and TCDD induced AHR binding to 127 common regions; however, there were significant differences in ligand (3MC vs. TCDD)-dependent AHR bound regions. The results illustrate the complexity of AHR signaling and also demonstrate that compared with TCDD as a reference ligand, 3MC is a selective AHR modulator.

Safe, Stephen

2010-01-01

126

Nondestructive testing of the human breast  

NASA Astrophysics Data System (ADS)

The utilization of thermal imaging in the evaluation of the human breast has been for the past two decades a highly effective form of screening for breast cancer and other breast disease. The procedure however, is not without controversy and a continuing debate concerning the competitive paradox with mammography as the gold standard in breast cancer screening/detection still exists. This paper and its accompanying oral presentation at Thermosense XXI will provide a brief historic overview of breast thermal imaging and will explore the authors concepts of the paradigm shift which needs to occur in order for breast thermal imaging to gain acceptance in the scientific, medical, and public communities. Early thermal imaging equipment sold for medical application were based on liquid crystal detector plates, or electronic low band infrared detectors. While the final output of these devices was quite colorful and impressive, they lacked the quantification necessary to accurately measure temperature from a medical perspective, and as such, many false positive findings and papers were produced which damaged the early credibility of the procedure. The author has previously suggested appropriate changes in both technology and in utilization protocol for correction of errors which have hindered the advancement and indeed, the further development and implementation of this most beneficial quantitative diagnostic tool.

Cockburn, William

1999-03-01

127

Caveolin-1 Mutations in Human Breast Cancer  

PubMed Central

A Japanese study reported that up to 16% of breast cancer samples harbor a sporadic mutation within the human Cav-1 gene, namely P132L. To date, however, no studies have examined the United States’ population. Here, we developed a novel allele-specific real-time PCR assay to detect the Cav-1 P132L mutation in mammary tumor cells isolated by laser capture microdissection from formalin-fixed paraffin-embedded breast cancer samples. We report that the Cav-1 P132L mutation is present in ?19% of estrogen receptor ? (ER?)-positive breast cancers but not in ER?-negative breast cancers. This is the first demonstration that the P132L mutation is exclusively associated with ER?-positive mammary tumors. We also identified six novel Cav-1 mutations associated with ER?-positive breast cancers (W128Stop, Y118H, S136R, I141T, Y148H, and Y148S). Thus, the overall incidence of Cav-1 mutations in ER?-positive breast cancers approaches 35% (greater than one-third). To mechanistically dissect the functional relationship between Cav-1 gene inactivation and ER? expression, we isolated primary mammary epithelial cells from wild-type and Cav-1?/? mice and cultured them in a three-dimensional system, allowing them to form mammary acinar-like structures. Under conditions of growth factor deprivation, Cav-1-deficient mammary acini displayed increased ER? levels and enhanced sensitivity toward estrogen-stimulated growth, with specific up-regulation of cyclin D1. Finally, we discuss the possibility that sporadic Cav-1 mutations may act as an initiating event in human breast cancer pathogenesis.

Li, Tianhong; Sotgia, Federica; Vuolo, Magalis A.; Li, Maomi; Yang, Wan Cai; Pestell, Richard G.; Sparano, Joseph A.; Lisanti, Michael P.

2006-01-01

128

Flecainide excretion in human breast milk  

Microsoft Academic Search

Healthy human volunteers who intended not to breast feed were placed on a regimen of 100 mg oral flecainide every 12 hours for 5½ days beginning 1 day after parturition. Milk and blood samples were collected during the dosing period and for 2 days after the last dose. Concentrations of flecainide in milk and plasma were assayed by HPLC. Apparent

Roy L McQuinn; Alison Pisani; Samir Wafa; Shaw F Chang; Aldora M Miller; Jonathan M Frappell; Geoffrey V P Chamberlain; A John Camm

1990-01-01

129

Retinol Esterification in Human Breast Cancer Cells.  

National Technical Information Service (NTIS)

This study was designed to identify the target genes of retinoids in the normal human mammary epithelial cells (HMEC) and breast cancer cells. In our early studies, we found that the IL-1Beta gene was a responsive gene to retinoic acid (RA) and its expres...

L. Liu

2003-01-01

130

Retinol Esterification in Human Breast Cancer Cells.  

National Technical Information Service (NTIS)

This study was designed to identify the RA target genes in the normal human mammary epithelial cells (HMEC) and breast cancer cells. We found that the IL-1Beta gene was an early responsive gene and its expression was up-regulated as early as two hours aft...

L. Liu

2002-01-01

131

Embryonic Morphogen Nodal Promotes Breast Cancer Growth and Progression  

PubMed Central

Breast cancers expressing human embryonic stem cell (hESC)-associated genes are more likely to progress than well-differentiated cancers and are thus associated with poor patient prognosis. Elevated proliferation and evasion of growth control are similarly associated with disease progression, and are classical hallmarks of cancer. In the current study we demonstrate that the hESC-associated factor Nodal promotes breast cancer growth. Specifically, we show that Nodal is elevated in aggressive MDA-MB-231, MDA-MB-468 and Hs578t human breast cancer cell lines, compared to poorly aggressive MCF-7 and T47D breast cancer cell lines. Nodal knockdown in aggressive breast cancer cells via shRNA reduces tumour incidence and significantly blunts tumour growth at primary sites. In vitro, using Trypan Blue exclusion assays, Western blot analysis of phosphorylated histone H3 and cleaved caspase-9, and real time RT-PCR analysis of BAX and BCL2 gene expression, we demonstrate that Nodal promotes expansion of breast cancer cells, likely via a combinatorial mechanism involving increased proliferation and decreased apopotosis. In an experimental model of metastasis using beta-glucuronidase (GUSB)-deficient NOD/SCID/mucopolysaccharidosis type VII (MPSVII) mice, we show that although Nodal is not required for the formation of small (<100 cells) micrometastases at secondary sites, it supports an elevated proliferation:apoptosis ratio (Ki67:TUNEL) in micrometastatic lesions. Indeed, at longer time points (8 weeks), we determined that Nodal is necessary for the subsequent development of macrometastatic lesions. Our findings demonstrate that Nodal supports tumour growth at primary and secondary sites by increasing the ratio of proliferation:apoptosis in breast cancer cells. As Nodal expression is relatively limited to embryonic systems and cancer, this study establishes Nodal as a potential tumour-specific target for the treatment of breast cancer.

Quail, Daniela F.; Zhang, Guihua; Walsh, Logan A.; Siegers, Gabrielle M.; Dieters-Castator, Dylan Z.; Findlay, Scott D.; Broughton, Heather; Putman, David M.; Hess, David A.; Postovit, Lynne-Marie

2012-01-01

132

HER2/neu Antisense Therapeutics in Human Breast Cancer.  

National Technical Information Service (NTIS)

In order to define mechanisms by which HER2/neu overexpression drives breast cancer cell growth and chemoresistance, antisense oligodeoxynucleotides (ODNs) have been used to down-regulate HER2/neu expression in human breast cancer cells. Such antisense OD...

J. A. Drebin

2002-01-01

133

TNF{alpha} acting on TNFR1 promotes breast cancer growth via p42/P44 MAPK, JNK, Akt and NF-{kappa}B-dependent pathways  

SciTech Connect

Tumor necrosis factor {alpha} (TNF{alpha}) enhances proliferation of chemically-induced mammary tumors and of T47D human cell line through not fully understood pathways. Here, we explored the intracellular signaling pathways triggered by TNF{alpha}, the participation of TNF{alpha} receptor (TNFR) 1 and TNFR2 and the molecular mechanism leading to breast cancer growth. We demonstrate that TNF{alpha} induced proliferation of C4HD murine mammary tumor cells and of T47D cells through the activation of p42/p44 MAPK, JNK, PI3-K/Akt pathways and nuclear factor-kappaB (NF-{kappa}B) transcriptional activation. A TNF{alpha}-specific mutein selectively binding to TNFR1 induced p42/p44 MAPK, JNK, Akt activation, NF-{kappa}B transcriptional activation and cell proliferation, just like wild-type TNF{alpha}, while a mutein selective for TNFR2 induced only p42/p44 MAPK activation. Interestingly, blockage of TNFR1 or TNFR2 with specific antibodies was enough to impair TNF{alpha} signaling and biological effect. Moreover, in vivo TNF{alpha} administration supported C4HD tumor growth. We also demonstrated, for the first time, that injection of a selective inhibitor of NF-{kappa}B activity, Bay 11-7082, resulted in regression of TNF{alpha}-promoted tumor. Bay 11-7082 blocked TNF{alpha} capacity to induce cell proliferation and up-regulation of cyclin D1 and of Bcl-x{sub L}in vivo and in vitro. Our results reveal evidence for TNF{alpha} as a breast tumor promoter, and provide novel data for a future therapeutic approach using TNF{alpha} antagonists and NF-{kappa}B pharmacological inhibitors in established breast cancer treatment.

Rivas, Martin A.; Carnevale, Romina P.; Proietti, Cecilia J.; Rosemblit, Cinthia; Beguelin, Wendy; Salatino, Mariana; Charreau, Eduardo H. [Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biologia y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires, C1428ADN (Argentina); Frahm, Isabel [Servicio de Patologia, Sanatorio Mater Dei, Buenos Aires (Argentina); Sapia, Sandra [Laboratorio de Patologia, Fundaleu, Buenos Aires (Argentina); Brouckaert, Peter [Department of Molecular Biomedical Research, VIB and Ghent University, Ghent (Belgium); Elizalde, Patricia V. [Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biologia y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires, C1428ADN (Argentina); Schillaci, Roxana [Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biologia y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires, C1428ADN (Argentina)], E-mail: rschilla@dna.uba.ar

2008-02-01

134

Genetic Screening Reveals an Essential Role of p27kip1 in Restriction of Breast Cancer Progression  

Microsoft Academic Search

The genetic changes and mechanisms underlying the prog- ression of estrogen-dependent breast cancers to estrogen- independent, antiestrogen-resistant, and metastatic breast cancers are unclear despite being a major problem in endocrine therapy. To identify genes responsible for this progression, we carried out a genetic screening by an enhanced retroviral mutagen (ERM)-mediated random mutagenesis in the estrogen-dependent T47D breast cancer cells. We

Yuhui Yuan; Li Qin; Ray-Chang Wu; Paola Mussi; Suoling Zhou; Zhou Songyang; Jianming Xu

2007-01-01

135

Receptor-selective retinoids inhibit the growth of normal and malignant breast cells by inducing G1 cell cycle blockade.  

PubMed

Despite advances in treatment, breast cancer continues to be the second leading cause of cancer mortality in women. Statistics suggest that while focus on treatment should continue, chemopreventive approaches should also be pursued. Previous studies have demonstrated that naturally occurring retinoids such as 9-cis retinoic acid (9cRA) can prevent breast cancer in animal models. However, these studies have also shown that these compounds are too toxic for general use. Work from our laboratory showed that an RXR-selective retinoid LGD1069 prevented tumor development in animal models of cancer with reduced toxicity as compared to an RAR-selective retinoid TTNPB. In the present study, we investigated the mechanisms by which receptor-selective retinoids inhibit the growth of normal and malignant breast cells. Our results demonstrate that the synthetic retinoids tested are as effective as 9cRA in suppressing the growth of normal human mammary epithelial cells (HMECs) and estrogen receptor-positive (ER-positive) breast cancer cells. Although the receptor-selective retinoids induce minimal amounts of apoptosis in T47D breast cancer cells, the predominant factor that leads to growth arrest is G1 cell cycle blockade. Our data indicate that this blockade results from the downregulation of Cyclin D1 and Cyclin D3, which in turn causes Rb hypophosphorylation. Non-toxic retinoids that are potent inducers of cell cycle arrest may be particularly useful for the prevention of breast cancer. PMID:16273314

Wu, Kendall; DuPré, Elizabeth; Kim, Heetae; Tin-U, Caesar K; Bissonnette, Reid P; Lamph, William W; Brown, Powel H

2005-11-05

136

Excretion of drugs in human breast milk  

SciTech Connect

The present report briefly discusses some of the morphological, physiological, and compositional aspects of animal and human breast milk and how these characteristics might be important for the accumulation of drugs and foreign compounds. In addition, a study is described confirming the presence of caffeine, codeine, morphine, phenacetin, acetaminophen, and salicylic acid in the breast milk of a lactating mother following oral administration of a combination analgesic containing aspirin, phenacetin, caffeine, and codeine. Although the study is limited to one subject, it has provided critically needed data on the rates of appearance in, and elimination of these drugs from, breast milk. A similar amount of information is presented on phenacetin, also a component of the analgesic mixture, which has not been previously reported to enter human milk. The distribution of these drugs between the slightly more acidic breast milk and the relatively neutral plasma is consistent with their weakly basic, acidic, or relatively neutral properties. In general, the study shows that codeine and morphine milk concentrations are higher than, salicylic acid milk levels are much lower than, and phenacetin, caffeine, and acetaminophen milk concentrations are relatively similar to their respective plasma levels. It is projected, from estimated steady-state milk concentrations of the drugs and their metabolites studied, that very low percentages of the therapeutic dosages (less than 0.7%) would be excreted in mother's milk, too low an amount to be clinically significant to the infant.

Welch, R.M.; Findlay, J.W.

1981-01-01

137

Excretion of drugs in human breast milk.  

PubMed

The present report briefly discusses some of the morphological, physiological, and compositional aspects of animal and human breast milk and how these characteristics might be important for the accumulation of drugs and foreign compounds. In addition, a study is described confirming the presence of caffeine, codeine, morphine, phenacetin, acetaminophen, and salicylic acid in the breast milk of a lactating mother following oral administration of a combination analgesic containing aspirin, phenacetin, caffeine, and codeine. Although the study is limited to one subject, it has provided critically needed data on the rates of appearance in, and elimination of these drugs from, breast milk. A similar amount of information is presented on phenacetin, also a component of the analgesic mixture, which has not been previously reported to enter human milk. The distribution of these drugs between the slightly more acidic breast milk and the relatively neutral plasma is consistent with their weakly basic, acidic, or relatively neutral properties. In general, the study shows that codeine and morphine milk concentrations are higher than, salicylic acid milk levels are much lower than, and phenacetin, caffeine, and acetaminophen milk concentrations are relatively similar to their respective plasma levels. It is projected, from estimated steady-state milk concentrations of the drugs and their metabolites studied, that very low percentages of the therapeutic dosages (less than 0.7%) would be excreted in mother's milk, too low an amount to be clinically significant to the infant. PMID:7040016

Welch, R M; Findlay, J W

1981-01-01

138

Chemical Biomarkers of Human Breast Milk Pollution  

PubMed Central

Human milk is, without question, the best source of nutrition for infants containing the optimal balance of fats, carbohydrates and proteins for developing babies. Breastfeeding provides a range of benefits for growth, immunity and development building a powerful bond between mother and her child. Recognition of the manifold benefits of breast milk has led to the adoption of breast-feeding policies by numerous health and professional organizations such as the World Health Organization and American Academy of Pediatrics. In industrially developed as well as in developing nations, human milk contamination by toxic chemicals such as heavy metals, dioxins and organohalogen compounds, however, is widespread and is the consequence of decades of inadequately controlled pollution. Through breastfeeding, the mother may transfer to the suckling infant potentially toxic chemicals to which the mother has previously been exposed. In the present review, environmental exposure, acquisition and current levels of old and emerging classes of breast milk pollutants are systematically presented. Although scientific evidences indicated that the advantages of breast-feeding outweigh any risks from contaminants, it is important to identify contaminant trends, to locate disproportionately exposed populations, and to take public health measures to improve chemical BM pollution as possible.

Massart, Francesco; Gherarducci, Giulia; Marchi, Benedetta; Saggese, Giuseppe

2008-01-01

139

The Terpenoid Tetrahydroisoquinoline Alkaloids Emetine, Klugine, and Isocephaeline Inhibit the Activation of Hypoxia-Inducible Factor-1 (HIF-1) in Breast Tumor Cells  

PubMed Central

Klugine (1), isocephaeline (2), and emetine (4) inhibited hypoxia-inducible factor-1 (HIF-1) activation by hypoxia in T47D breast tumor cells (IC50 values 0.2, 1.1, and 0.11 µM, respectively). Compounds 1, 2, and 4 inhibited both hypoxia- and iron chelator-induced HIF-1 activation by blocking HIF-1? protein accumulation.

Zhou, Yu-Dong; Kim, Yong-Pil; Mohammed, Kaleem Asjad; Jones, Deborah K.; Muhammad, Ilias; Dunbar, D. Chuck; Nagle, Dale G.

2010-01-01

140

Shu-Gan-Liang-Xue Decoction Simultaneously Down-regulates Expressions of Aromatase and Steroid Sulfatase in Estrogen Receptor Positive Breast Cancer Cells  

PubMed Central

Objective Estradiol (E2) plays an important role in the development of breast cancer. In postmenopausal women, the estrogen can be synthesized via aromatase (CYP19) pathway and steroid-sulfatase (STS) pathway in peripheral tissues, when the production in ovary has ceased. The objective of our study was to explore the effects of Shu-Gan-Liang-Xue Decoction (SGLXD) on the expressions of CYP19 and STS in estrogen receptor positive breast cancer MCF-7 and T47D cells. Methods The effects of SGLXD on the cell viability of MCF-7 and T47D were analyzed by MTT assay. By quantitative real-time RT-PCR and Western blot, we evaluated the mRNA and protein expressions of CYP19 and STS in MCF-7 and T47D cells after SGLXD treatment. Results By MTT assay, the cell viability rates of MCF-7 and T47D were significantly inhibited by SGLXD in a dose-dependent manner, the IC50 values were 40.07 mg/ml for MCF-7 cells and 25.62 mg/ml for T47D cells, respectively. As evidenced by real-time PCR and Western blot, the high concentrations of SGLXD significantly down-regulated the expressions of CYP19 and STS both in the transcript level and the protein level. Conclusion The results suggest that SGLXD is a potential dual aromatase-sulfatase inhibitor by simultaneously down-regulating the expressions of CYP19 and STS in MCF-7 and T47D cells.

Fu, Xue-song; Li, Ping-ping

2011-01-01

141

Crosstalk between PKC? and Notch-4 in endocrine-resistant breast cancer cells  

PubMed Central

The Notch pathway is functionally important in breast cancer. Notch-1 has been reported to maintain an estrogen-independent phenotype in estrogen receptor ? (ER?)+ breast cancer cells. Notch-4 expression correlates with Ki67. Notch-4 also plays a key role in breast cancer stem-like cells. Estrogen-independent breast cancer cell lines have higher Notch activity than estrogen-dependent lines. Protein kinase C? (PKC?) overexpression is common in endocrine-resistant breast cancers and promotes tamoxifen (TAM)-resistant growth in breast cancer cell lines. We tested whether PKC? overexpression affects Notch activity and whether Notch signaling contributes to endocrine resistance in PKC?-overexpressing breast cancer cells.Analysis of published microarray data from ER?+ breast carcinomas shows that PKC? expression correlates strongly with Notch-4. Real-time reverse transcription PCR and immunohistochemistry on archival specimens confirmed this finding. In a PKC?-overexpressing, TAM-resistant T47D model, PKC? selectively increases Notch-4, but not Notch-1, expression in vitro and in vivo. This effect is mediated by activator protein-1 (AP-1) occupancy of the Notch-4 promoter. Notch-4 knockdown inhibits estrogen-independent growth of PKC?-overexpressing T47D cells, whereas Notch-4IC expression stimulates it. Gene expression profiling shows that multiple genes and pathways associated with endocrine resistance are induced in Notch-4IC- and PKC?-expressing T47D cells. In PKC?-overexpressing T47D xenografts, an orally active ?-secretase inhibitor at clinically relevant doses significantly decreased estrogen-independent tumor growth, alone and in combination with TAM. In conclusion, PKC? overexpression induces Notch-4 through AP-1. Notch-4 promotes estrogen-independent, TAM-resistant growth and activates multiple pathways connected with endocrine resistance and chemoresistance. Notch inhibitors should be clinically evaluated in PKC?- and Notch-4-overexpressing, endocrine-resistant breast cancers.

Yun, J; Pannuti, A; Espinoza, I; Zhu, H; Hicks, C; Zhu, X; Caskey, M; Rizzo, P; D'Souza, G; Backus, K; Denning, M F; Coon, J; Sun, M; Bresnick, E H; Osipo, C; Wu, J; Strack, P R; Tonetti, D A; Miele, L

2013-01-01

142

Defining the cellular precursors to human breast cancer  

PubMed Central

Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues.

Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

2012-01-01

143

Lump detection in simulated human breasts  

Microsoft Academic Search

Sixteen observers palpated silicone models of human breasts containing lumps 1.6-12.1 mm in diameter. Detectability depended\\u000a on the size of the lump, producing a systematic psychometric function. In eight observers who participated in three or more\\u000a sessions, performance improved with practice, with most improvement occurring within one or two 26-trial sessions. Three-week\\u000a retention measures disclosed no appreciable decrease in performance,

Calvin K. Adams; Deborah C. Hall; H. S. Pennypacker; Mark Kane Goldstein; Larry L. Hench; Michael C. Madden; Gerald H. Stein; A. Charles Catania

1976-01-01

144

A monoclonal antibody to the human c-erbB3 protein stimulates the anchorage-independent growth of breast cancer cell lines.  

PubMed Central

The c-erbB3 protein is a member of the type I growth factor receptor family. It has a widespread pattern of expression in normal tissues and is overexpressed in about 20% of breast cancers. We have raised a specific monoclonal antibody, called SGP1, against the extracellular domain of c-erbB3 which recognises the native form of the protein. The monoclonal antibody was found to modestly but significantly stimulate the anchorage-independent cloning efficiency of the breast tumour cell lines BT483 and T47D, both of which express the c-erbB3 protein. No effect was observed on 293 cells lacking expression, nor did a control isotype-matched antibody promote the growth of any of the cells tested. These results suggest that the c-erbB3 protein may normally act as a growth factor receptor. Images Figure 1 Figure 2 Figure 3 Figure 6

Rajkumar, T.; Gullick, W. J.

1994-01-01

145

Local regulation of human breast xenograft models  

PubMed Central

Breast cancer studies implant human cancer cells under the renal capsule, subcutaneously, or orthotopically and often use estrogen supplementation and immune suppressants (etoposide) in xenograft mouse models. However, cell behavior is significantly impacted by signals from the local microenvironment. Therefore, we investigated how the combinatorial effect of the location of injection and procedural differences affected xenograft characteristics. Patient-derived breast cancer cells were injected into mouse abdominal or thoracic mammary glands ± estrogen and/or etoposide pretreatment. Abdominal xenografts had increased tumor incidence and volume, and decreased latency (P<0.001) compared to thoracic tumors. No statistically significant difference in tumor volume was found in abdominal xenografts treated ± estrogen or etoposide; however, etoposide suppressed tumor volume in thoracic xenografts (P<0.02). The combination of estrogen and etoposide significantly decreased tumor incidence in both sites. In addition, mice treated ± estradiol were injected orthotopically or subcutaneously with well-characterized breast cancer cell lines (MCF7, ZR75-1, MDA MB-231, or MCF10Ca1h). Orthotopic injection increased tumor volume; growth varied with estrogen supplementation. Location also altered methylation status of several breast cancer-related gene promoters. Lastly, vascularization of orthotopic tumors was significantly enhanced compared to subcutaneous tumors. These data suggest that optimal xenograft success occurs with orthotopic abdominal injections and illustrate molecular details of the compelling influence of the local microenvironment on in vivo models.

Fleming, Jodie M.; Miller, Tyler C.; Meyer, Matthew J.; Ginsburg, Erika; Vonderhaar, Barbara K.

2010-01-01

146

Terminal Differentiation of Human Breast Cancer through PPAR?  

Microsoft Academic Search

We have previously demonstrated that PPAR? stimulates the terminal differentiation of adipocyte precursors when activated by synthetic ligands, such as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPAR? is expressed at significant levels in human primary and metastatic breast adenocarcinomas. Ligand activation of this receptor in cultured breast cancer cells causes extensive lipid accumulation, changes in breast epithelial

Elisabetta Mueller; Pasha Sarraf; Peter Tontonoz; Ronald M. Evans; Katherine J. Martin; Ming Zhang; Christopher Fletcher; Samuel Singer; Bruce M. Spiegelman

1998-01-01

147

Autocrine and paracrine growth regulation of human breast cancer  

Microsoft Academic Search

Summary We consider the hypothesis that estrogen control of hormone dependent breast cancer is mediated by autocrine and paracrine growth factors secreted by the breast cancer cells themselves. Though we show direct, unmediated effects of estrogen on specific cell functions, we also provide evidence that human breast cancer cells secrete a collection of growth factors (IGF-I, TGFa, TGFß, a PDGF-like

Marc E. Lippman; Robert B. Dickson; Susan Bates; Cornelius Knabbe; Karen Huff; Sandra Swain; Mary McManaway; Diane Bronzert; Attan Kasid; Edward P. Gelmann

1986-01-01

148

Modelling defined mixtures of environmental oestrogens found in domestic animal and sewage treatment effluents using an in vitro oestrogen-mediated transcriptional activation assay (T47D-KBluc  

EPA Science Inventory

There is growing concern that exposure of fish, wildlife, and humans to water sources contaminated with estrogens could potentially impact reproductive health. Environmental estrogens can come from various sources including concentrated animal feedlot operations (CAFO), municipal...

149

Modeling the interaction of binary and ternary mixtures of estradiol with bisphenol A and bisphenol A F in an in vitro estrogen mediated transcriptional activation assay (T47D-KBluc).  

EPA Science Inventory

Humans are concurrently exposed to xenoestrogens and to physiological levels of endogenous estrogens. Endogenous estrogen levels vary from low levels in infants to high levels during pregnancy and in young women. However, few studies have addressed how xenoestrogens interact with...

150

Expression of biomarkers related to cell adhesion, metastasis and invasion of breast cancer cell lines of different molecular subtype.  

PubMed

Aim:The aim of our study was to determine the complex of molecular genetic markers which are associated with cancer aggressiveness, invasion and metastasis among different molecular subtypes of breast cancer cell lines. Materials and Methods: The cell lines used in the analysis include T47D, MCF-7, MDA-MB-231, MDA-MB-468, MCF-10A and 184A1. Expression of estrogen receptor, progesterone receptor, Her-2/neu and Ki-67 was studied by immunocytochemical method. CD24, CD44 and E-cadherin expression was studied by flow cytometry. Results: We have identified biomarkers which characterize metastatic potential of human breast cancer cells of certain molecular subtypes. It has been demonstrated that low colony forming activity of human breast cancer cells of luminal subtype is accompanied by increased adhesive properties of these cells due to high level of E-cadherin expression, low level of CD44 expression and absence of CD24 expression. High tumorigenicity of cells of basal subtype is connected to weakening of adhesive contacts that is caused by abnormalities of E-cadherin expression, significant increase of CD44 expression and presence of low level of CD24 expression. Conclusion: Our data indicated that changes of correlation between expression of cellular adhesion molecules inside conventional immunohistochemical subtypes reflect significantly wider biological properties of luminal and basal subtypes of human breast cancer. PMID:24084454

Chekhun, S; Bezdenezhnykh, N; Shvets, J; Lukianova, N

2013-09-01

151

Involvement of a Human Endogenous Retrovirus in Breast Cancer.  

National Technical Information Service (NTIS)

We are testing the hypothesis that human mammary tumor virus (HMTV), a human endogenous retrovirus (HERV) closely related to mouse mammary tumor virus (MMTV), is etiologically involved in a subset of human breast cancers. We continue to collect blood and ...

R. F. Garry

2001-01-01

152

Regulation of nuclear receptor and cofactor expression in breast cancer cell lines  

Microsoft Academic Search

Objective: The aim of this study was to compare the expression profile of nuclear receptors (NRs) and cofactors in different breast cancer cell lines as well as their regulation by estradiol, insulin and pro- gestin R5020. Methods: Expression of NRs and cofactors were determined from MCF-7, T-47D and ZR-75-1 breast cancer cell lines. Multiprobe ribonuclease protection assay and real-time RT-PCR

Annika Vienonen; Susanna Miettinen; Tommi Manninen; Lucia Altucci; Emmanuelle Wilhelm; Timo Ylikomi

2003-01-01

153

Novel radiolabeled peptides for breast and prostate tumor PET imaging: (64)Cu/and (68)Ga/NOTA-PEG-[D-Tyr(6),?Ala(11),Thi(13),Nle(14)]BBN(6-14).  

PubMed

Bombesin (BBN)-based radiolabeled peptides exhibit promising properties for targeted imaging of gastrin-releasing peptide receptors (GRPR)-positive tumors. The aim of this study was to evaluate with positron emission tomography (PET) the pharmacokinetic and imaging properties of two novel BBN-based radiolabeled peptides, (64)Cu/and (68)Ga/NOTA-PEG-BBN(6-14), for diagnosis of breast and prostate cancers using small animal models. Competitive binding assays on T47D breast and PC3 prostate cancer cells showed that the affinity for GRPR depends on the complexed metal and can vary up to a factor of about 3; (64)Cu/NOTA-PEG-BBN(6-14) was found to have the lowest inhibition constant (1.60 ± 0.59 nM). (64)Cu/and (68)Ga/NOTA-PEG-BBN(6-14) presented similar cell uptake on T47D and PC3 cells and were stable in vivo. Biodistribution studies of radiolabeled peptides carried out in Balb/c and tumor-bearing Balb/c nude mice showed that (64)Cu/NOTA-PEG-BBN(6-14) presented higher GRPR-mediated uptake in pancreas and adrenal glands, but comparable PC3 tumor uptake as (68)Ga/NOTA-PEG-BBN(6-14). Finally, receptor-dependent responses were observed during blocking studies with unlabeled peptide in both biodistribution and small-animal PET imaging studies. Our results confirmed the dependence of the affinity and pharmacokinetics of BBN-based radiopeptides on the complexed radiometal. Interspecies differences between mouse and human GRPR binding properties were also noted in these preclinical studies. Considering their good imaging characteristics, both (64)Cu/NOTA-PEG-BBN(6-14) and (68)Ga/NOTA-PEG-BBN(6-14) are promising candidates for GRPR-targeted PET imaging of breast and prostate cancers. PMID:22770480

Fournier, Patrick; Dumulon-Perreault, Véronique; Ait-Mohand, Samia; Tremblay, Sébastien; Bénard, François; Lecomte, Roger; Guérin, Brigitte

2012-07-25

154

ODAM Expression Inhibits Human Breast Cancer Tumorigenesis  

PubMed Central

We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.

Kestler, Daniel P.; Foster, James S.; Bruker, Charles T.; Prenshaw, John W.; Kennel, Stephen J.; Wall, Jonathan S.; Weiss, Deborah T.; Solomon, Alan

2011-01-01

155

Metallothionein expression in human breast cancer.  

PubMed Central

Metallothioneins are ubiquitous low molecular weight proteins characterised by high cysteine content and affinity for binding heavy metals. Abnormal metallothionein function and expression have been implicated in various disease states, including neoplasia. The aim of this study was to investigate metallothionein expression in human breast carcinoma. Sections of routinely fixed and processed blocks of tumour from 100 consecutive cases of primary operable breast carcinoma were stained for metallothionein using a recently developed monoclonal antibody and a standard immunohistochemical technique. Expression was scored on the basis of microscopical assessment of percentage of tumour cells staining. One patient was lost to follow-up and excluded from the study. A significant association (P < 0.0001) was observed between metallothionein expression and tumour type, with low levels being observed in tumours of good prognostic type. There was also a significant association with local recurrence (P < 0.02) and a significant difference (P < 0.02) in both survival and disease-free interval between tumours showing low and high levels of expression, the latter indicating a poor prognosis. No relationship was observed with patient age, tumour size, lymph node stage, histological grade, vascular invasion, menopausal status or oestrogen receptor status. The assessment of metallothionein expression in human breast cancer appears to provide prognostic information and may have important implications for understanding its development. Images Figure 1 Figure 2

Goulding, H.; Jasani, B.; Pereira, H.; Reid, A.; Galea, M.; Bell, J. A.; Elston, C. W.; Robertson, J. F.; Blamey, R. W.; Nicholson, R. A.

1995-01-01

156

The role of human papillomavirus infection in breast cancer  

Microsoft Academic Search

Breast cancer is the leading female cancer and the third most common cause of cancer deaths worldwide. Many studies have suggested\\u000a a possible link between breast cancer pathogenesis and viral infection, particularly mouse mammary tumour virus, simian virus\\u000a 40, Epstein–Barr virus, and human papillomavirus (HPV). A significant number of recent studies have reported that approximately\\u000a 29% of human breast cancer

Ting WangPeng; Peng Chang; Ling Wang; Qing Yao; Wen Guo; Jianghao Chen; Tristan Yan; Christopher Cao

157

Excretion of loratadine in human breast milk.  

PubMed

The excretion of loratadine, a new nonsedating antihistamine, into human breast milk was studied in six lactating nonpregnant volunteers. Each volunteer received one 40-mg loratadine capsule. Milk and blood were collected before and at specified times (to 48 hours) after dosing. Plasma and milk loratadine concentrations were determined by a specific radioimmunoassay, and those of an active but minor metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Breast milk concentration-time curves of both loratadine and descarboethoxyloratadine paralleled the plasma concentration-time curves. For loratadine, the plasma Cmax was 30.5 ng/mL at 1.0 hour after dosing and the milk Cmax was 29.2 ng/mL in the 0 to 2 hour collection interval. Through 48 hours, the loratadine milk-plasma AUC ratio was 1.2 and 4.2 micrograms of loratadine was excreted in breast milk, which was 0.010% of the administered dose. For descarboethoxyloratadine, the plasma Cmax was 18.6 ng/mL at 2.2 hours after dosing, whereas the milk Cmax was 16.0 ng/mL, which was in the 4 to 8-hour collection interval. Through 48 hours, the mean milk-plasma descarboethoxyloratadine AUC ratio was 0.8 and a mean of 6.0 micrograms of descarboethoxyloratadine (7.5 micrograms loratadine equivalents) were excreted in the breast milk, or 0.019% of the administered loratadine dose. Thus, a total of 11.7 micrograms loratadine equivalents or 0.029% of the administered dose were excreted as loratadine and its active metabolite. A 4-kg infant ingesting the loratadine and descarboethoxyloratadine excreted would receive a dose equivalent to 0.46% of the loratadine dose received by the mother on a mg/kg basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2966185

Hilbert, J; Radwanski, E; Affrime, M B; Perentesis, G; Symchowicz, S; Zampaglione, N

1988-03-01

158

Involvement of a Human Endogenous Retrovirus in Breast Cancer.  

National Technical Information Service (NTIS)

Our overall goal is to determine whether human mammary tumor virus (HMTV) sequences, present as an endogenous retrovirus, are involved in a subset of human breast cancers. In studies completed for first specific aim, samples form a cohort (>200) of breast...

R. F. Garry

2003-01-01

159

Microdissection and microcloning of chromosomal alterations in human breast cancer  

Microsoft Academic Search

The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic

Jeffrey M. Trent; Barbara Weber; X. Y. Guan; Ji Zhang; Francis Collins; Ken Abel; Austin Diamond; Paul Meltzer

1995-01-01

160

The Gene Expression Response of Breast Cancer to Growth Regulators: Patterns and Correlation with Tumor Expression Profiles  

Microsoft Academic Search

The effects of hormone and growth factor signaling on gene expression contribute significantly to breast tumorigenesis and disease progression; however, the targets of signaling networks associated with deregulated growth are not well understood. We defined the dynamic transcriptional effects elicited in MCF7, T-47D, and MDA-MB-436 breast cancer cell lines by nine regulators of growth and differentiation (17-estradiol, antiestro- gens fulvestrant

Heather E. Cunliffe; Markus Ringner; Sven Bilke; Robert L. Walker; Jennifer M. Cheung; Yidong Chen; Paul S. Meltzer

161

Role of p53 in Human Breast Cancer.  

National Technical Information Service (NTIS)

The principal objectives are to: (1) Transfect p53 mutants commonly observed in human breast cancer into normal human mammary epithelial cells obtained from different donors and isolate clones; (2) Characterize the clones for extension of lifespan and imm...

J. W. Shay

1996-01-01

162

CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells.  

PubMed

The aim of this current study was to examine the significance of CD44 expression in mediating cancer cell adhesion to human bone marrow endothelial cell(s) (hBMEC). Differential CD44 expression on two metastatic prostate cancer cell lines, PC3 (CD44 +ve) and DU145 (CD44 -ve) and four breast cancer cell lines was confirmed by immunoblotting and immunocytochemistry. In cell adhesion assays, PC3 but not DU145 cells demonstrated a rapid adhesion to hBMECs. Treatment of PC3 cells with a neutralizing antibody against CD44 standard (CD44s) and CD44 splice variants decreased PC3 cell adhesion to hBMECs. Similarly, depletion of CD44 expression using RNA interference decreased the ability of PC3 cells and two CD44 +ve breast cancer cell lines (MDA-MB-231 and MDA-MB-157) to bind FITC-conjugated hyaluronan (FITC-HA) and to adhere to hBMECs. In contrast, transfection of DU145 cells or the T47D and MCF-7 breast cancer cell lines to express CD44s increased cell surface binding of FITC-HA and cell adherence to hBMECs. Treatment of PC3 and MDA-MD-231 cells but not hBMECs with hyaluronidase attenuated cell adhesion, suggesting that cell surface expression of CD44 on prostate and breast cancer cells may promote the retention of a HA coat that facilitates their initial arrest on bone marrow endothelium. PMID:15313910

Draffin, Jayne E; McFarlane, Suzanne; Hill, Ashleigh; Johnston, Patrick G; Waugh, David J J

2004-08-15

163

Extra-Nuclear Signalling of Estrogen Receptor to Breast Cancer Cytoskeletal Remodelling, Migration and Invasion  

PubMed Central

Background Estrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted. Methodology/Principal Findings In estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17?-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER? with the G protein G?13, which results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G?13/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane. Conclusions/Significance These results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G?13/RhoA/ROCK/moesin signaling cascade as a target of ER? in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions.

Giretti, Maria Silvia; Fu, Xiao-Dong; De Rosa, Giovanni; Sarotto, Ivana; Baldacci, Chiara; Garibaldi, Silvia; Mannella, Paolo; Biglia, Nicoletta; Sismondi, Piero; Genazzani, Andrea Riccardo; Simoncini, Tommaso

2008-01-01

164

Anterior gradient-2 plays a critical role in breast cancer cell growth and survival by modulating cyclin D1, estrogen receptor-? and survivin  

PubMed Central

Introduction Anterior-gradient 2 (AGR2) is an estrogen-responsive secreted protein. Its upregulation has been well documented in a number of cancers, particularly breast cancer, for which mixed data exist on the prognostic implications of AGR2 expression. Although emerging evidence indicates that AGR2 is associated with poor prognosis, its function and impact on cancer-relevant pathways have not been elucidated in breast cancer. Methods To investigate the biologic role of AGR2 in breast cancer, AGR2 was transiently knocked down, by using siRNA, in T47 D and ZR-75-1 (estrogen receptor-? (ER)-positive) and MDA-MB-231 and SK-BR-3 (ER-negative) human breast cancer cell lines. The impact of silencing AGR2 was evaluated in both anchorage-dependent and anchorage-independent growth (soft agar, spheroid) assays. Cell-cycle profiles in ER-positive cell lines were determined with BrdU incorporation, and cell death was measured with Annexin V, JC-1, and F7-26 staining. After transiently silencing AGR2 or stimulating with recombinant AGR2, modulation of key regulators of growth and survival pathways was assessed with Western blot. Combination studies of AGR2 knockdown with the antiestrogens tamoxifen and fulvestrant were carried out and assessed at the level of anchorage-dependent growth inhibition and target modulation (cyclin D1, ER). Results AGR2 knockdown inhibited growth in anchorage-dependent and anchorage-independent assays, with a more-pronounced effect in ER-positive cell lines. Cyclin D1 levels and BrdU incorporation were reduced with AGR2 knockdown. Conversely, cyclin D1 was induced with recombinant AGR2. AGR2 knockdown induced cell death in ZR-75-1 and T47 D cells, and also downregulated survivin and c-Myc. Evidence of AGR2-ER crosstalk was demonstrated by a reduction of ER at the protein level after transiently silencing AGR2. AGR2 knockdown in combination with fulvestrant or tamoxifen did not preclude the efficacy of the antiestrogens, but enhanced it. In addition, p-Src, implicated in tamoxifen resistance, was downregulated with AGR2 knockdown. Conclusions Transiently silencing AGR2 in ER-positive breast cancer cell lines inhibited cell growth and cell-cycle progression and induced cell death. Breast cancer drivers (ER and cyclin D1) as well as cancer-signaling nodes (pSrc, c-Myc, and survivin) were demonstrated to be downstream of AGR2. Collectively, the data presented support the utility of anti-AGR2 therapy in ER-positive breast cancers because of its impact on cancer-relevant pathways.

2010-01-01

165

Cacospongionolide and Scalaradial, Two Marine Sesterterpenoids as Potent Apoptosis-Inducing Factors in Human Carcinoma Cell Lines  

PubMed Central

Apoptosis, a form of programmed cell death, is a critical defence mechanism against the formation and progression of cancer and acts by eliminating potentially deleterious cells without causing such adverse effects, as inflammatory response and ensuing scar formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. In last decades, marine natural products, such as sesterterpenoids, have played an important role in the discovery and development of new drugs. Interestingly, many of these compounds have a strong potential as anticancer drugs by inhibiting cell proliferation and/or inducing cell death. In the present study, we investigated the effects of scalaradial and cacospongionolide, two sesterterpenoids from Cacospongia scalaris and Fasciospongia cavernosa marine sponges, on the apoptotic signalling pathway in three different human tumoral cells. Results were obtained by using DNA fragmentation, comet and viability assays, quantification of the mitochondrial transmembrane potential and Western blot. The T47D (human breast carcinoma), A431 (human epidermoid carcinoma), HeLa (human cervix carcinoma) and HCT116 (human colon carcinoma) cells were incubated for 24 h with scalaradial or cacospongionolide. Treatment of T47D cells with scalaradial or cacospongionolide for 24 h brought about a significant increase in DNA migration as well as fragmentation. Moreover, incubation of HCT116 and HeLa cells with scalaradial or cacospongionolide for 24 h caused an increased expression of pro-apoptotic proteins. Furthermore, scalaradial or cacospongionolide, added to HCT116 and HeLa cells overnight, induced a significant and concentration-dependent loss of mitochondrial transmembrane potential, an early apoptosis signalling event. These effects paralleled with those achieved with p50 and p65, NF-?B subunits, nuclear level. In conclusion, scalaradial and cacospongionolide, by determining human cancer cell apoptosis, may represent new promising compounds to inhibit cancer cell proliferation.

Malik, Shoaib Ahmad; Iodice, Carmine; De Rosa, Salvatore; Maiuri, Maria Chiara; Carnuccio, Rosa

2012-01-01

166

Low frequency of human papillomavirus DNA in breast cancer tissue  

Microsoft Academic Search

Human papillomavirus (HPV) is considered the aetiological agent for cervical cancer. Several reports have addressed a relationship\\u000a with HPV and breast cancer, as different HPVs have been identified. The purpose of this study was to detect HPV DNA in 67\\u000a breast cancer patients and 40 non-malignant disease breast tissues by means of Polymerase Chain Reaction with consensus primers.\\u000a The frequency

A. P. Mendizabal-Ruiz; J. A. Morales; L. J. Ramírez-Jirano; M. Padilla-Rosas; M. C. Morán-Moguel; H. Montoya-Fuentes

2009-01-01

167

Integrin activation controls metastasis in human breast cancer  

NASA Astrophysics Data System (ADS)

Metastasis is the primary cause of death in human breast cancer. Metastasis to bone, lungs, liver, and brain involves dissemination of breast cancer cells via the bloodstream and requires adhesion within the vasculature. Blood cell adhesion within the vasculature depends on integrins, a family of transmembrane adhesion receptors, and is regulated by integrin activation. Here we show that integrin v3 supports breast cancer cell attachment under blood flow conditions in an activation-dependent manner. Integrin v3 was found in two distinct functional states in human breast cancer cells. The activated, but not the nonactivated, state supported tumor cell arrest during blood flow through interaction with platelets. Importantly, activated ?v?3 was expressed by freshly isolated metastatic human breast cancer cells and variants of the MDA-MB 435 human breast cancer cell line, derived from mammary fat pad tumors or distant metastases in severe combined immunodeficient mice. Expression of constitutively activated mutant ?v?3D723R, but not ?v?3WT, in MDA-MB 435 cells strongly promoted metastasis in the mouse model. Thus breast cancer cells can exhibit a platelet-interactive and metastatic phenotype that is controlled by the activation of integrin ?v?3. Consequently, alterations within tumors that lead to the aberrant control of integrin activation are expected to adversely affect the course of human breast cancer.

Felding-Habermann, Brunhilde; O'Toole, Timothy E.; Smith, Jeffrey W.; Fransvea, Emilia; Ruggeri, Zaverio M.; Ginsberg, Mark H.; Hughes, Paul E.; Pampori, Nisar; Shattil, Sanford J.; Saven, Alan; Mueller, Barbara M.

2001-02-01

168

Lubricin in human breast tissue expander capsules.  

PubMed

Capsular contraction is the most common complication of breast reconstruction surgery. While presence of the contractile protein alpha smooth muscle actin (?-SMA) is considered among the causes of capsular contraction, the exact etiology and pathophysiology is not fully understood. The objective of this study was to investigate the possible role of lubricin in capsular formation and contraction by determining the presence and distribution of the lubricating protein lubricin in human breast tissue expander capsules. Related aims were to evaluate select histopathologic features of the capsules, and the percentage of cells expressing ?-SMA, which reflects the myofibroblast phenotype. Capsules from tissue expanders were obtained from eight patients. Lubricin, at the tissue-implant interface, in the extracellular matrix, and in cells, and ?-SMA-containing cells were evaluated immunohistochemically. The notable finding was that lubricin was identified in all tissue expander capsules: as a discrete layer at the tissue-implant interface, extracellular, and intracellular. There was a greater amount of lubricin in the extracellular matrix in the intimal-subintimal zone when compared with the tissue away from the implant. Varying degrees of synovial metaplasia were seen at the tissue-implant interface. ?-SMA-containing cells were also seen in all but one patient. The findings might help us better understand factors involved in capsule formation. PMID:22865664

Cheriyan, Thomas; Guo, Lifei; Orgill, Dennis P; Padera, Robert F; Schmid, Thomas M; Spector, Myron

2012-08-04

169

Synthesis of novel 4-(1H-benzimidazol-2-yl)benzene-1,3-diols and their cytotoxic activity against human cancer cell lines.  

PubMed

One-pot synthesis of new biologically active 4-(1H-benzimidazol-2-yl)benzene-l,3-diols has been developed. The compounds were prepared by the reaction of aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s with benzene-l,2-diamines. Their structures were identified using elemental, IR, (1)H-NMR, and mass spectra analyses. The developed method offers short reaction times, relatively large-scale synthesis, easy and quick isolation of the products, and good yields. The cytotoxicity in vitro against the 4 human cancer cell lines: SW707 (rectal), HCV29T (bladder), A549 (lung), and T47D (breast) was determined. The antiproliferative properties of some compounds studies were stronger than those of cisplatin, which was used as a comparator drug. PMID:22076764

Karpi?ka, Monika M; Matysiak, Joanna; Niewiadomy, Andrzej

2011-11-12

170

1,25-Dihydroxyvitamin D3 and All-trans-Retinoic Acid Sensitize Breast Cancer Cells to Chemotherapy-induced Cell Death1  

Microsoft Academic Search

We investigated the capacity of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and all-trans-retinoic acid (ATRA) to sensitize three breast cancer cell lines to the cell killing effects of paclitaxel (Taxol) and Adriamycin, two chemother- apeutic agents commonly used in the treatment of breast cancer. In tissue culture colony assays, 1,25(OH)2D3 and ATRA were synergistic in inhibiting the clonogenicity of MCF-7 and T-47D cells

Qin Wang; Wen Yang; Myrna S. Uytingco; Sylvia Christakos; Robert Wieder

171

Role of AKT2 in Human Breast Cancer.  

National Technical Information Service (NTIS)

Frequent alterations of AKT2 oncogene have been frequently detected in human malignancies, including breast carcinoma (1, 2). To better understand the role of AKT2 in breast carcinogenesis, we have isolated a novel protein, APBP, that binds to and is phos...

Z. Q. Yuan J. Q. Cheng

2002-01-01

172

Role of cdc25 Phosphatases in Human Breast Cancer.  

National Technical Information Service (NTIS)

A summary is presented of research performed during the second year of a project to determine the role of Cdc25 phosphatases in human breast cancer. The research involves three specific aims. In the first aim, the role of Cdc25B in breast cancer prolifera...

J. J. Manfredi

2007-01-01

173

Integrin activation controls metastasis in human breast cancer  

Microsoft Academic Search

Metastasis is the primary cause of death in human breast cancer. Metastasis to bone, lungs, liver, and brain involves dissemination of breast cancer cells via the bloodstream and requires adhesion within the vasculature. Blood cell adhesion within the vasculature depends on integrins, a family of transmembrane adhesion receptors, and is regulated by integrin activation. Here we show that integrin v3

Brunhilde Felding-Habermann; Timothy E. O'Toole; Jeffrey W. Smith; Emilia Fransvea; Zaverio M. Ruggeri; Mark H. Ginsberg; Paul E. Hughes; Nisar Pampori; Sanford J. Shattil; Alan Saven; Barbara M. Mueller

2001-01-01

174

The Basic Pathology of Human Breast Cancer  

Microsoft Academic Search

This article illustrates the most common benign and malignant lesions in the breast, and is intended for the biologist working in the area of breast cancer and breast biology, not for the practicing pathologist. The atlas covers benign proliferative lesions, atypical lesions, variants of in situ cancer, the main types of invasive cancers, spindle cell lesions, and examples of vascular

Elizabeth Mallon; Pinchas Osin; Nasar Nasiri; Iain Blain; Beatrice Howard; Barry Gusterson

2000-01-01

175

Biocompatibility of Fe3O4 nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells  

NASA Astrophysics Data System (ADS)

In order to reveal the biocompatibility of Fe3O4 nanoparticles and bipolar surfactant tetramethylammonium 11-aminoundecanoate cytotoxicity tests were performed as a function of concentration from low (0.1 µg ml-1) to higher concentration (100 µg ml-1) using various human glia, human breast cancer and normal cell lines. Cytotoxicity tests for human glia (D54MG, G9T, SF126, U87, U251, U373), human breast cancer (MB157, SKBR3, T47D) and normal (H184B5F5/M10, WI-38, SVGp12) cell lines exhibited almost nontoxicity and reveal biocompatibility of Fe3O4 nanoparticles in the concentration range of 0.1-10 µg ml-1, while accountable cytotoxicity can be seen at 100 µg ml-1. The results of our studies suggest that Fe3O4 nanoparticles coated with bipolar surfactant tetramethylammonium 11-aminoundecanoate are biocompatible and promising for bio-applications such as drug delivery, magnetic resonance imaging and magnetic hyperthermia.

Ankamwar, B.; Lai, T. C.; Huang, J. H.; Liu, R. S.; Hsiao, M.; Chen, C. H.; Hwu, Y. K.

2010-02-01

176

Repression of Lim only protein 4-activated transcription inhibits proliferation and induces apoptosis of normal mammary epithelial cells and breast cancer cells.  

PubMed

Lim only protein (LMO) 4 acts as a transcriptional adapter and modulates mammary gland morphogenesis as well as breast oncogenesis in transgenic mice. Yet, the molecular and cellular mechanisms of these effects remain to be fully elucidated. Engrailed LMO4 fusion protein is a powerful dominant repressor of LMO4 activated transcription that was successfully used to discover the role of LMO4 as a transcriptional activator in mammary gland development in our previous studies using mouse models. In this manuscript, we investigated the cellular effects of LMO4 in human normal mammary epithelial cells (HMECs) and breast cancer cell lines using the Engrailed-LMO4 fusion protein. HMEC cell growth was inhibited by the expression of the Engrailed-LMO4 fusion protein. The decrease in cell number was due to both decreased cell proliferation and enhanced apoptosis, suggesting that LMO4 promotes proliferation and survival of normal mammary epithelial cells. The expression of the Engrailed-LMO4 fusion protein also suppressed cell growth, and induced apoptosis in two breast cancer cell lines, MDA-MB-231 and T47D, suggesting that LMO4 contributes to oncogenesis by similar mechanisms of enhanced cell survival and proliferation. Taken together, our data indicate that LMO4 has similar cellular effects in normal mammary epithelial cells and breast cancer cells, and also provide direct evidence for the idea that normal development and carcinogenesis share conserved molecular mechanisms. PMID:20526802

Tian, Yingpu; Wang, Ning; Lu, Zhongxian

2010-06-06

177

Interactions of vitamin D analogue CB1093, TNF? and ceramide on breast cancer cell apoptosis  

Microsoft Academic Search

Mechanisms by which vitamin D analogues promote apoptosis in tumour cells are unclear. In this study we have examined possible interactions between the synthetic vitamin D analogue CB1093 and two other known mediators of apoptosis, TNF? and ceramide, in MCF-7, T47D and Hs578T breast cancer cells. These studies indicated that cytosolic phospholipase A2 (cPLA2) is involved in CB1093 as well

G Pirianov; K. W Colston

2001-01-01

178

Characterization of Gene Expression in Human Breast Tumor Endothelium.  

National Technical Information Service (NTIS)

Angiogenesis is the growth of new capillary blood vessels, and is a critical component of solid tumor growth. We characterized molecular changes between human breast tumor vessels and normal vessels to identify genes that may serve as therapeutic targets....

N. Klauber-DeMore

2008-01-01

179

Detection of human mammary tumor virus proteins in human breast cancer cells  

Microsoft Academic Search

Mouse mammary tumor virus (MMTV) has been proven to induce mammary cancer in mice. MMTV-like env gene sequences have been detected in one-third of the human breast tumors studied. The whole proviral structure with 95% homology to MMTV was found in two human breast tumors and was designated as human mammary tumor virus (HMTV). HMTV viral particles with betaretroviral features

Stella M. Melana; Irene Nepomnaschy; Jennifer Hasa; Alina Djougarian; Anna Djougarian; James F. Holland; Beatriz G. T. Pogo

2010-01-01

180

Steroid Receptors, Stem Cells and Proliferation in the Human Breast  

Microsoft Academic Search

This review summarises the current evidence for adult tissue stem cells in the human breast and examines the role of stemcells,\\u000a steroids and self-renewal signalling pathways in normal human breast development. The development of the mammary gland is\\u000a a complex and lengthy process, beginning during embryogenesis and not reaching full functionality until pregnancy and lactation.\\u000a The gland goes through massive

Hannah Harrison; Rebecca Lamb; Robert B. Clarke

181

A Mechanistic Study of the Effect of Doxorubicin/Adriamycin on the Estrogen Response in a Breast Cancer Model  

PubMed Central

Objective Estrogen treatment limits the cytotoxic effects of chemotherapy in estrogen receptor-positive (ER+) breast cancer cell lines, suggesting that estrogen-pathway signaling may confer chemotherapeutic resistance. This study investigates the molecular responses of ER+ breast cancer cell lines to the chemotherapeutic agent, doxorubicin, in the presence or absence of estrogen. Methods ER+ MCF-7 and T47-D cells were cultured in hormone-starved or estrogen-containing media with or without doxorubicin at concentrations mimicking the low concentrations seen in plasma and tumor microenvironments in humans following typical bolus administration. Protein levels, phosphorylations, and interactions of estrogen-signaling molecules were assessed following these treatments, as well the effects of ER signaling inhibitors on cell proliferation. Results Surprisingly, estrogen and doxorubicin co-treatment markedly induced pro-growth alterations compared to doxorubicin alone and modestly enhanced estrogen alone-induced changes. Several inhibitors suppressed cell proliferation in the presence of doxorubicin and estrogen. Conclusions These findings demonstrate that molecular changes caused by doxorubicin in ER+ breast cancer cells can be reversed by estrogen, providing molecular evidence for the poorer responses of ER+ tumors to doxorubicin in the presence of physiologic estrogen levels. Our results also suggest that the addition of drugs targeting the ER, EGFR, the SFKs, MEK, PI3K, and/or the MMP proteins to a conventional chemotherapy regimen may improve chemosensitivity.

Pritchard, Jessica E.; Dillon, Patrick M.; Conaway, Mark R.; Silva, Corinne M.; Parsons, Sarah J.

2013-01-01

182

Involvement of a Human Endogenous Retrovirus in Breast Cancer.  

National Technical Information Service (NTIS)

The genomic DNA of a subset of humans contains an endogenous retrovirus closely related to mouse mammary tumor virus (MWTV) . Our overall goal is to determine whether the human mammary tumor virus (HMTV) sequences are involved in a subset of human breast ...

R. F. Garry

2002-01-01

183

Specific Recruitment of ?? Regulatory T Cells in Human Breast Cancer.  

PubMed

Understanding the role of different subtypes of tumor-infiltrating lymphocytes (TIL) in the immunosuppressive tumor microenvironment is essential for improving cancer treatment. Enriched ??1 T-cell populations in TILs suppress T-cell responses and dendritic cell maturation in breast cancer, where their presence is correlated negatively with clinical outcomes. However, mechanism(s) that explain the increase in this class of regulatory T cells (?? Treg) in patients with breast cancer have yet to be elucidated. In this study, we show that IP-10 secreted by breast cancer cells attracted ?? Tregs. Using neutralizing antibodies against chemokines secreted by breast cancer cells, we found that IP-10 was the only functional chemokine that causes ?? Tregs to migrate toward breast cancer cells. In a humanized NOD-scid IL-2R?(null) (NSG) mouse model, human breast cancer cells attracted ?? Tregs as revealed by a live cell imaging system. IP-10 neutralization in vivo inhibited migration and trafficking of ?? Tregs into breast tumor sites, enhancing tumor immunity mediated by tumor-specific T cells. Together, our studies show how ?? Tregs accumulate in breast tumors, providing a rationale for their immunologic targeting to relieve immunosuppression in the tumor microenvironment. Cancer Res; 73(20); 6137-48. ©2013 AACR. PMID:23959855

Ye, Jian; Ma, Chunling; Wang, Fang; Hsueh, Eddy C; Toth, Karoly; Huang, Yi; Mo, Wei; Liu, Shuai; Han, Bing; Varvares, Mark A; Hoft, Daniel F; Peng, Guangyong

2013-08-19

184

Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide.  

PubMed

Concentrations of the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) in human breast milk are important indicators of infant formula DHA and AA concentrations, and recent evidence suggests that neural maturation of breastfed infants is linked to breast-milk LCPUFA concentrations. We report a descriptive meta-analysis that considered 106 studies of human breast milk culled to include only studies that used modern analysis methods capable of making accurate estimates of fatty acid (FA) profiles and criteria related to the completeness of reporting. The final analysis included 65 studies of 2474 women. The mean (+/-SD) concentration of DHA in breast milk (by wt) is 0.32 +/- 0.22% (range: 0.06-1.4%) and that of AA is 0.47 +/- 0.13% (range: 0.24-1.0%), which indicates that the DHA concentration in breast milk is lower than and more variable than that of AA. The highest DHA concentrations were primarily in coastal populations and were associated with marine food consumption. The correlation between breast-milk DHA and AA concentrations was significant but low (r = 0.25, P = 0.02), which indicates that the mean ratio of DHA to AA in regional breast milk varies widely. This comprehensive analysis of breast-milk DHA and AA indicates a broad range of these nutrients worldwide and serves as a guide for infant feeding. PMID:17556680

Brenna, J Thomas; Varamini, Behzad; Jensen, Robert G; Diersen-Schade, Deborah A; Boettcher, Julia A; Arterburn, Linda M

2007-06-01

185

Rhein Induces Apoptosis in Human Breast Cancer Cells  

PubMed Central

Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2) and control vector MCF-7 (MCF-7/VEC) cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-?B- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

Chang, Ching-Yao; Chan, Hong-Lin; Lin, Hui-Yi; Way, Tzong-Der; Kao, Ming-Ching; Song, Ming-Zhang; Lin, Ying-Ju; Lin, Cheng-Wen

2012-01-01

186

Comparison of the antiproliferative activity of crude ethanol extracts of nine salvia species grown in Jordan against breast cancer cell line models  

PubMed Central

Background: The antiproliferative activity of Salvia species grown in Jordan has not been fully evaluated yet. The aim of this work was to study the antiproliferative activity of crude ethanol extracts from nine Salvia species grown in Jordan against a panel of breast cancer cell lines. Material and Methods: Cytotoxic activity was evaluated in human tumor models of breast cancer; MCF-7, T47D, ZR-75-1, and BT 474 by the sulforhodamine B assay. In addition, the extracts were evaluated using a non-transformed cell line (Vero) and normal fibroblast cells in order to demonstrate their selectivity and safety. Results: From the nice ethanol extracts under investigation, those of S. dominica and S. fruticosa showed an inhibitory concentration of 50% of cells (IC50) in concentrations less than 30?g/mL against the four cell lines under investigation. S. syriaca and S. hormium showed an IC50 below 30?g/ml for two out of the four cell lines. S. fruticosa, S. hormium and S. syriaca showed selectivity in their antiproliferative activity against estrogen receptor positive cell lines with minimal toxicity against normal human periodontal fibroblasts. Phytochemical screening using thin layer chromatography indicated the presence of terpenoids, flavonoids and coumarins in all examined extracts. Conclusion: Three of the plant extracts under investigation exhibited antiproliferative activity against breast cancer cells and were shown to be safe and selective. These could be considered as a potential source for novel anticancer therapy.

Abu-Dahab, Rana; Afifi, Fatma; Kasabri, Violet; Majdalawi, Lara; Naffa, Randa

2012-01-01

187

Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT)  

Microsoft Academic Search

Bone marrow-derived mesenchymal stem cells (MSCs) are known to specifically migrate to and engraft at tumour sites. Understanding\\u000a interactions between cancer cells and MSCs has become fundamental to determining whether MSC-tumour interactions should be\\u000a harnessed for delivery of therapeutic agents or considered a target for intervention. Breast Cancer Cell lines (MDA-MB-231,\\u000a T47D & SK-Br3) were cultured alone or on a

F. T. Martin; R. M. Dwyer; J. Kelly; S. Khan; J. M. Murphy; C. Curran; N. Miller; E. Hennessy; P. Dockery; F. P. Barry; T. O’Brien; M. J. Kerin

2010-01-01

188

Epithelial mesenchymal transition traits in human breast cancer cell lines  

Microsoft Academic Search

Epithelial mesenchymal transition (EMT) has long been associated with breast cancer cell invasiveness and evidence of EMT\\u000a processes in clinical samples is growing rapidly. Genome-wide transcriptional profiling of increasingly larger numbers of\\u000a human breast cancer (HBC) cell lines have confirmed the existence of a subgroup of cell lines (termed Basal B\\/Mesenchymal)\\u000a with enhanced invasive properties and a predominantly mesenchymal gene

T. Blick; E. Widodo; H. Hugo; M. Waltham; M. E. Lenburg; R. M. Neve; E. W. Thompson

2008-01-01

189

Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells  

PubMed Central

Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A) or breast cancer cells (MDA-MB-231 and MCF7). We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS) level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

Warleta, Fernando; Quesada, Cristina Sanchez; Campos, Maria; Allouche, Yosra; Beltran, Gabriel; Gaforio, Jose J.

2011-01-01

190

Peripheral Benzodiazepine Receptor (PBR) in Human Breast Cancer.  

National Technical Information Service (NTIS)

The peripheral-type benzodiazepine receptor (PBR) is an 18 kDa high affinity cholesterol and drug binding protein, part of the aggressive human breast cancer cell phenotype in vitro. We report herein that in human biopsies elevated PBR expression is limit...

V. Papadopoulas

2003-01-01

191

Comprehensive molecular portraits of human breast tumors  

PubMed Central

Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.

2012-01-01

192

Comprehensive molecular portraits of human breast tumours.  

PubMed

We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer. PMID:23000897

2012-09-23

193

Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways.  

PubMed

ABSTRACT: INTRODUCTION: Mammary-specific overexpression of Six1 in mice induces tumors that resemble human breast cancer, some having undergone epithelial to mesenchymal transition (EMT) and exhibiting stem/progenitor cell features. Six1 overexpression in human breast cancer cells promotes EMT and metastatic dissemination. We hypothesized that Six1 plays a role in the tumor initiating cell (TIC) population specifically in certain subtypes of breast cancer, and that by understanding its mechanism of action, we could potentially develop new means to target TICs. METHODS: We examined gene expression datasets to determine the breast cancer subtypes with Six1 overexpression, and then examined its expression in the CD24low/CD44+ putative TIC population in human luminal breast cancers xenografted through mice and in luminal breast cancer cell lines. Six1 overexpression, or knockdown, was performed in different systems to examine how Six1 levels affect TIC characteristics, using gene expression and flow cytometric analysis, tumorsphere assays, and in vivo TIC assays in immunocompromised and immune-competent mice. We examined the molecular pathways by which Six1 influences TICs using genetic/inhibitor approaches in vitro and in vivo. Finally, we examined the expression of Six1 and phosphorylated extracellular signal-regulated kinase (p-ERK) in human breast cancers. RESULTS: High levels of Six1 are associated with adverse outcomes in luminal breast cancers, particularly the luminal B subtype. Six1 levels are enriched in the CD24low/CD44+ TIC population in human luminal breast cancers xenografted through mice, and in tumorsphere cultures in MCF7 and T47D luminal breast cancer cells. When overexpressed in MCF7 cells, Six1expands the TIC population through activation of transforming growth factor-beta (TGF-?) and mitogen activated protein kinase (MEK)/ERK signaling. Inhibition of ERK signaling in MCF7-Six1 cells with MEK1/2 inhibitors, U0126 and AZD6244, restores the TIC population of luminal breast cancer cells back to that observed in control cells. Administration of AZD6244 dramatically inhibits tumor formation efficiency and metastasis in cells that express high levels of Six1 ectopically or endogenously. Finally, we demonstrate that Six1 significantly correlates with phosphorylated ERK in human breast cancers. CONCLUSIONS: Six1 plays an important role in the TIC population in luminal breast cancers and induces a TIC phenotype by enhancing both TGF-? and ERK signaling. MEK1/2 kinase inhibitors are potential candidates for targeting TICs in breast tumors. PMID:22765220

Iwanaga, Ritsuko; Wang, Chu-An; Micalizzi, Douglas S; Harrell, J Chuck; Jedlicka, Paul; Sartorius, Carol A; Kabos, Peter; Farabaugh, Susan M; Bradford, Andrew P; Ford, Heide L

2012-07-01

194

microRNA, Cell Cycle, and Human Breast Cancer  

PubMed Central

The discovery of microRNAs as a novel class of gene expression regulators has led to a new strategy for disease diagnostics and therapeutics. Cell cycle, cell proliferation, and tumorigenesis are all regulated by microRNAs. Several general principles linking microRNAs and cancer have been recently reviewed; therefore, the current review focuses specifically on the perspective of microRNAs in control of cell cycle, stem cells, and heterotypic signaling, as well as the role of these processes in breast cancer. Altered abundance of cell cycle regulation proteins and aberrant expression of microRNAs frequently coexist in human breast cancers. Altered microRNA expression in breast cancer cell lines is associated with altered cell cycle progression and cell proliferation. Indeed, recent studies have demonstrated a causal role for microRNA in governing breast tumor suppression or collaborative oncogenesis. This review summarizes the current understanding of the role for microRNA in regulating the cell cycle and summarizes the evidence for aberrant microRNA expression in breast cancer. The new evidence for microRNA regulation by annotated genes and the involvement of microRNA in breast cancer metastasis are discussed, as is the potential for microRNA to improve breast cancer diagnosis and therapy.

Yu, Zuoren; Baserga, Renato; Chen, Lide; Wang, Chenguang; Lisanti, Michael P.; Pestell, Richard G.

2010-01-01

195

Cytotoxicity of fucosterol containing fraction of marine algae against breast and colon carcinoma cell line  

PubMed Central

Context: Marine algae produce different secondary metabolites with a wide range of biological activities. Many studies have been achieved on the screening of biological effects of marine organisms and a lot of active compounds were isolated and characterized. Aims: In an attempt to find cytotoxic compound of hexane fraction, isolation, identification, and cytotoxicity of active compound of this fraction were performed. Materials and Methods: In this study, total methanolic (70%) extract and partition fractions of hexane, chloroform (CHCl3), ethyl acetate (EtOAc), and MeOH–H2O of Sargassum angustifolium, Chondria dasyphylla, and Ulva flexuosa, collected from coastlines of the Persian Gulf in south of Iran, were studied against colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), and Swiss mouse embryo fibroblast (NIH 3T3) cell lines by MTT assay. Statistical Analysis Used: IC50 (median growth inhibitory concentration) values were calculated by Sigmaplot (10) software. Results: Hexane fraction of Chondria dasyphylla (IC50 82.26 ± 4.09 ?g/ml) and MeOH-H2O fraction of Ulva flexuosa (IC50 116.92 ± 8.58 ?g/ml) showed cytotoxic activity against proliferation of T47D cells. Hexane fraction of Sargassum angustifolium was also observed for cytotoxicity against T47D and HT-29 cell lines (IC50 166.42 ± 26.7 and 190.24 ± 52.8 ?g/ml), respectively. An investigation of a component from the hexane fraction of Sargassum angustifolium yielded a steroidal metabolite, fucosterol, with cytotoxicity in T47D and HT29 (IC50 27.94 ± 9.3 and 70.41 ± 7.5 ?g/ml). Conclusions: These results indicated that fucosterol, the most abundant phytosterol in brown algae, is responsible for cytotoxic effect of this extract against breast and colon carcinoma cell lines.

Khanavi, Mahnaz; Gheidarloo, Razieh; Sadati, Nargess; Ardekani, Mohammad Reza Shams; Nabavi, Seyed Mohammad Bagher; Tavajohi, Shohreh; Ostad, Seyed Nasser

2012-01-01

196

Proteolysis in human breast and colorectal cancer.  

PubMed

Proteolysis occurs when proteinase activity exceeds inhibitor activity. Proteolysis is normally tightly regulated and is involved in cancer invasion and metastasis. The aim of this study was to compare proteolysis in breast and colorectal cancer. Proteinase and inhibitor expression were analysed in paired tumour and normal tissue samples from 43 breast and 24 colorectal cancer patients using substrate zymography, Western blotting and quenched fluorescence substrate hydrolysis. The expression of the latent forms of matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, urokinase plasminogen activator (uPA), tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression were observed in both tumour and normal tissue samples from breast and colorectal tissue; however, expression was greater in the tumour tissue. Expression of active MMP-2 and MMP-9 and the total MMP activity were greater in tumour compared to normal samples in both tissues (P < 0.05). The expression of all proteinases and total MMP activity was greater in colorectal tissue than breast tissue samples. Breast and colorectal cancer demonstrated different proteinase profiles, however proteolysis in both tissues was greater in tumour tissue than normal tissue. PMID:10496354

Garbett, E A; Reed, M W; Brown, N J

1999-09-01

197

AIB1 Cooperates with ER? to Promote Epithelial Mesenchymal Transition in Breast Cancer through SNAI1 Activation  

PubMed Central

Epithelial Mesenchymal Transition (EMT) plays a major role in cancer metastasis. Several genes have been shown to play a role in EMT, and one of these is Amplified-in-breast cancer 1 (AIB1), which has oncogenic function and is known to be amplified in breast cancer. However, the role of AIB1 in EMT remains largely undefined at the molecular level. In this study, the effect of AIB1 overexpression on the EMT of the breast cancer cell line T47D was investigated. Overexpression of AIB1 disrupted the epithelial morphology of the cells. At the same time, the cells displayed a strong metastasis and reduced level of the epithelial marker E-cadherin. In contrast, knockdown of AIB1 in T47D cells increased cell-cell adhesion and produced weak metastasis, as well as a higher level of E-cadherin expression. We proposed that the regulation of EMT by AIB1 occurred through the action of the transcription factor SNAI1, and demonstrated that such interaction required the participation of ER? and the presence of ER?-binding site on SNAI1 promoter. The expression level of E-cadherin and the extent of cell migration and invasion in SNAI1-knocked down T47D cells that overexpressed AIB1 were similar to those of T47D cells that did not overexpress AIB1 and had no SNAI1 knockdown. Taken together, these results suggested that AIB1 exerted its effect on EMT through its interaction with ER?, which could directly bind to the ER?-binding site on the SNAI1 promoter, allowing the AIB1-ER? complex to promote the transcription of SNAI1 and eventually led to repression of E-cadherin expression, consistent with the loss of E-cadherin being a hallmark of EMT.

Wang, Miao; Zhao, Feng; Li, Shujing; Chang, Alan K.; Jia, Zhaojun; Chen, Yixuan; Xu, Feihong; Pan, Hongming; Wu, Huijian

2013-01-01

198

Identification of human papillomavirus DNA gene sequences in human breast cancer.  

PubMed

Human papilloma viruses (HPVs) are accepted as being carcinogenic in human cervical and anogenital cancers. The suspicion that HPVs may also have a role in human breast cancer is based on the identification of HPVs in human breast tumours and the immortalisation of normal human breast cells by HPV types 16 and 18. For this investigation, DNA that had been previously extracted and fresh frozen at -70 degrees C from 50 unselected invasive ductal breast cancer specimens were screened by polymerase chain reaction (PCR) for HPV type 16, 18 and 33 gene sequences. We show that HPV 18 gene sequences are present in DNA extracted from breast tumours in Australian women. Overall, 24 (48%) of the 50 samples were HPV positive. Overall no correlations with tumour grade, patient survival, steroid receptor status, ERB-2, p53 expression and mutation were observed. Human papilloma viruses may have a role in human breast cancer. We speculate that HPVs may be transmitted by hand from the female perineum to the breast. PMID:16222323

Kan, C-Y; Iacopetta, B J; Lawson, J S; Whitaker, N J

2005-10-17

199

Characterization of Viral Particles Isolated from Primary Cultures of Human Breast Cancer Cells  

Microsoft Academic Search

The association of human breast cancer with sequences similar to the mouse mammary tumor virus (MMTV) has been shown, but convincing evidence for the presence of viral particles in breast tumors has been lacking. We have described the complete proviral structure of a retrovirus in human breast cancer. This provirus, designated as human mammary tumor virus (HMTV), was 95% homologous

Stella M. Melana; Irene Nepomnaschy; Michael Sakalian; Andrea Abbott; Jennifer Hasa; James F. Holland

200

Caveolin-1 expression in human breast lobular cancer progression  

Microsoft Academic Search

Caveolin-1 is the principal structural protein of caveolae, and caveolin-1 gene plays a role as a tumour suppressor gene in human mammary cancer-derived cells. However, limited data are available concerning caveolin-1 expression in human breast cancer tissue. We evaluated caveolin-1 expression in normal lobular epithelial cells and in the whole human lobular neoplasia spectrum disease, with the aim to examine

Giuseppe Perrone; Vittorio Altomare; Mariagiovanna Zagami; Sergio Morini; Tommaso Petitti; Cleonice Battista; Andrea Onetti Muda; Carla Rabitti

2009-01-01

201

Oestradiol and basic fibroblast growth factor stimulate expression of very low density lipoprotein receptor and plasminogen activator inhibitor-1 in breast carcinoma cell lines  

Microsoft Academic Search

Two breast carcinoma cell lines were tested for modulation of expression of PAI-1 and endocytosis receptors of the low-density lipoprotein receptor family by oestradiol and basic fibroblast growth factor (bFGF). Oestradiol and bFGF induced very low-density lipoprotein receptor (VLDLR) in T47D cells, but not in MCF-7 cells. The cell-specific splice variation of VLDLR mRNA was not changed by oestradiol and

B. Madsen; P. M. Martensen; A. Christensen; P. A. Andreasen

1999-01-01

202

Prolactin Overexpression by MDA-MB-435 Human Breast Cancer Cells Accelerates Tumor Growth  

Microsoft Academic Search

Prolactin (PRL) is an important hormone in mammary tumorigenesis in rodents but its involvement in human breast cancer has been controversial. A role for locally produced PRL in breast carcinogenesis is suggested by its mitogenic action on breast cancer cells and the expression of both PRL and its receptor (PRL-R) in breast carcinomas. Our objective was to examine whether PRL,

Karen Liby; Bonnie Neltner; Lisa Mohamet; Lindsey Menchen; Nira Ben-Jonathan

2003-01-01

203

A putative human breast stem cell population is enriched for steroid receptor-positive cells  

Microsoft Academic Search

Breast epithelial stem cells are thought to be the primary targets in the etiology of breast cancer. Since breast cancers mostly express estrogen and progesterone receptor (ER? and PR), we examined the biology of these ER?\\/PR-positive cells and their relationship to stem cells in normal human breast epithelium. We employed several complementary approaches to identify putative stem cell markers, to

Robert B. Clarke; Katherine Spence; Elizabeth Anderson; Anthony Howell; Hideyuki Okano; Christopher S. Potten

2005-01-01

204

Human mammaglobin RT-PCR assay for detection of occult breast cancer cells in hematopoietic products  

Microsoft Academic Search

Materials and methods: A nested RT-PCR assay for mammaglobin was developed. Sensitivity was determined by serial dilution assays with breast cancer cell lines, human breast cancers and normal breast tissue. Specificity was evaluated in hematopoietic samples from healthy volunteers and patients with hematological malignancies or solid tumors other than breast cancer. Results: The mammaglobin transcript was detected in all 15

A. L. Silva; M. J. Tomé; A. E. Correia; J. L. Passos-Coelho

2002-01-01

205

CT-X antigen expression in human breast cancer.  

PubMed

Cancer/testis (CT) genes are predominantly expressed in human germ line cells, but not somatic tissues, and frequently become activated in different cancer types. Several CT antigens have already proved to be useful biomarkers and are promising targets for therapeutic cancer vaccines. The aim of the present study was to investigate the expression of CT antigens in breast cancer. Using previously generated massively parallel signature sequencing (MPSS) data, together with 9 publicly available gene expression datasets, the expression pattern of CT antigens located on the X chromosome (CT-X) was interrogated. Whereas a minority of unselected breast cancers was found to contain CT-X transcripts, a significantly higher expression frequency was detected in estrogen and progesterone receptor (ER) negative breast cancer cell lines and primary breast carcinomas. A coordinated pattern of CT-X antigen expression was observed, with MAGEA and NY-ESO-1/CTAG1B being the most prevalent antigens. Immunohistochemical staining confirmed the correlation of CT-X antigen expression and ER negativity in breast tumors and demonstrated a trend for their coexpression with basal cell markers. Because of the limited therapeutic options for ER-negative breast cancers, vaccines based on CT-X antigens might prove to be useful. PMID:19651608

Grigoriadis, Anita; Caballero, Otavia L; Hoek, Keith S; da Silva, Leonard; Chen, Yao-Tseng; Shin, Sandra J; Jungbluth, Achim A; Miller, Lance D; Clouston, David; Cebon, Jonathan; Old, Lloyd J; Lakhani, Sunil R; Simpson, Andrew J G; Neville, A Munro

2009-07-27

206

CT-X antigen expression in human breast cancer  

PubMed Central

Cancer/testis (CT) genes are predominantly expressed in human germ line cells, but not somatic tissues, and frequently become activated in different cancer types. Several CT antigens have already proved to be useful biomarkers and are promising targets for therapeutic cancer vaccines. The aim of the present study was to investigate the expression of CT antigens in breast cancer. Using previously generated massively parallel signature sequencing (MPSS) data, together with 9 publicly available gene expression datasets, the expression pattern of CT antigens located on the X chromosome (CT-X) was interrogated. Whereas a minority of unselected breast cancers was found to contain CT-X transcripts, a significantly higher expression frequency was detected in estrogen and progesterone receptor (ER) negative breast cancer cell lines and primary breast carcinomas. A coordinated pattern of CT-X antigen expression was observed, with MAGEA and NY-ESO-1/CTAG1B being the most prevalent antigens. Immunohistochemical staining confirmed the correlation of CT-X antigen expression and ER negativity in breast tumors and demonstrated a trend for their coexpression with basal cell markers. Because of the limited therapeutic options for ER-negative breast cancers, vaccines based on CT-X antigens might prove to be useful.

Grigoriadis, Anita; Caballero, Otavia L.; Hoek, Keith S.; da Silva, Leonard; Chen, Yao-Tseng; Shin, Sandra J.; Jungbluth, Achim A.; Miller, Lance D.; Clouston, David; Cebon, Jonathan; Old, Lloyd J.; Lakhani, Sunil R.; Simpson, Andrew J. G.; Neville, A. Munro

2009-01-01

207

Spectral imaging of the human breast for quantitative oximetry  

NASA Astrophysics Data System (ADS)

We developed a hybrid continuous-wave/frequency-domain instrument to obtain both spatial and spectral information of the female breast. The two-dimensional (2D) tandem planar scanning of a compressed breast enables a pixel size of 2×2 mm2 and a continuous spectra acquisition from 650 nm to 900 nm at every image pixel with a 0.5 nm spectral step. A 2D spline interpolation algorithm is implemented to increase the data sampling rate and reduce the pixel size to 0.5×0.5 mm2. We then apply an edge-correction method to compensate the signal change due to the breast thickness variation. The resulted optical density image is further processed using a previously developed second-derivative algorithm to enhance the contrast and improve the spatial resolution of the optical inhomogeneities within the breast tissue. The finer structures displayed in the second-derivative image offer better identification of the pixels of interest associated with significant hemoglobin presence. We then employ a novel paired-wavelength oximetry method to determine the absolution value of oxygen saturation for those identified pixels of interest. We found the majority of oxygen saturation values from two healthy human subjects fall within the range 60%-95%, which is consistent with previously published results. Breast oximetry could have a potential applicability toward breast cancer detection and diagnostics and this novel paired-wavelength method can be a robust and accurate way to retrieve the oxygenation information in vivo.

Yu, Yang; Liu, Ning; Sassaroli, Angelo; Fantini, Sergio

2009-02-01

208

Immunity to Murine Breast Cancer Cells Modified to Express MUC1, a Human Breast Cancer Antigen, in Transgenic Mice Tolerant to Human MUC11  

Microsoft Academic Search

The high incidence of breast cancer in women and the severity of the disease have stimulated a need for improved and novel forms of therapy. The product of the MUC-1 gene has been identified as a breast cancer- associated antigen in breast cancer patients. The gene has been cloned and sequenced. Transgenic mice were prepared that express human mucin and

Victoria Carr-Brendel; Dubravka Markovic; Karen Ferrer; Michael Smith; Joyce Taylor-Papadimitriou; Edward P. Cohen

209

Paclitaxel Combined with Inhibitors of Glucose and Hydroperoxide Metabolism Enhances Breast Cancer Cell Killing Via H2O2-Mediated Oxidative Stress  

PubMed Central

Cancer cells (relative to normal cells) demonstrate alterations in oxidative metabolism characterized by increased steady-state levels of reactive oxygen species [i.e. hydrogen peroxide, H2O2] that may be compensated for by increased glucose metabolism but the therapeutic significance of these observations is unknown. In the current study, inhibitors of glucose [i.e., 2-deoxy-D-glucose, 2DG] and hydroperoxide [i.e., L-buthionine-S, R-sulfoximine, BSO] metabolism were utilized in combination with a chemotherapeutic agent paclitaxel [PTX], thought to induce oxidative stress, to treat breast cancer cells. 2DG+PTX were found to be more toxic than either agent alone in T47D and MDA-MB231 human breast cancer cells, but not in normal human fibroblasts or normal human mammary epithelial cells. Increases in parameters indicative of oxidative stress, including steady-state levels of H2O2, total glutathione, and glutathione disulfide accompanied the enhanced toxicity of 2DG+PTX in cancer cells. Antioxidants, including N-acetyl-cysteine [NAC], polyethylene glycol-conjugated catalase [PEG-CAT] and superoxide dismutase [PEG-SOD], inhibited the toxicity of 2DG+PTX and suppressed parameters indicative of oxidative stress in cancer cells, while inhibition of glutathione synthesis using BSO further sensitized breast cancer cells to 2DG+PTX. These results show that combining inhibitors of glucose [2DG] and hydroperoxide [BSO] metabolism with PTX selectively (relative to normal cells) enhances breast cancer cell killing via H2O2-induced metabolic oxidative stress, and suggests that this biochemical rationale may be effectively utilized to treat breast cancers.

Hadzic, Tanja; Aykin-Burns, Nukhet; Zhu, Yueming; Coleman, Mitchell C.; Leick, Katie; Jacobson, Geraldine M.; Spitz, Douglas R.

2010-01-01

210

Role of Basic Fibroblast Growth Factor in Human Breast Cancer.  

National Technical Information Service (NTIS)

We found that basic fibroblast growth factor (bFGF), a mitogen, inhibits human breast cancer cell lines. In MCF-7 cells, bFGF binds high-affinity tyrosine kinase FGF receptors (FGFR), activates MAP kinase, induces higher levels of G(1) cyclins D1 and E an...

R. Wieder

1995-01-01

211

Total prolactin binding sites in human breast cancer biopsies  

Microsoft Academic Search

Summary Total and free prolactin receptors were assayed in 72 human breast tumor biopsies. Forty-nine percent of the tumors are positive (specific binding greater than 0.8% of total radioactivity) when assaying free receptors, while 71% are positive when total receptors levels are determined. No clear relationship exists between the prolactin receptor positivity and the presence of either progesterone or estradiol

J. P. Peyrat; D. Dewailly; J. Djiane; P. A. Kelly; B. Vandewalle; J. Bonneterre; J. Lefebvre

1981-01-01

212

Retrotransposons as Mutagens in Human Breast Cancer. Addendume.  

National Technical Information Service (NTIS)

It is known that the human LINE-1 retrotransposon (L1Hs) is transcriptionally active in many breast cancer cells. The original goal of the project was to test the possibility that L1Hs retrotransposition events result in the inactivation of tumor suppress...

T. G. Fanning

2000-01-01

213

The Consensus Coding Sequences of Human Breast and Colorectal Cancers  

Microsoft Academic Search

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average

Tobias Sjöblom; Siân Jones; Laura D. Wood; D. Williams Parsons; Jimmy Lin; Thomas D. Barber; Diana Mandelker; Rebecca J. Leary; Janine Ptak; Natalie Silliman; Steve Szabo; Phillip Buckhaults; Christopher Farrell; Paul Meeh; Sanford D. Markowitz; Joseph Willis; Dawn Dawson; James K. V. Willson; Adi F. Gazdar; James Hartigan; Leo Wu; Changsheng Liu; Giovanni Parmigiani; Ben Ho Park; Kurtis E. Bachman; Nickolas Papadopoulos; Bert Vogelstein; Kenneth W. Kinzler; Victor E. Velculescu

2006-01-01

214

Expression of different proteoglycans in human breast tumors.  

PubMed

The composition of proteoglycans and their changes during malignant transformation are important factors influencing adhesive properties and mitotic activity of tumor cells. In this study, expression level of different proteoglycans (decorin, syndecan-1, lumican, glypican-1, and aggrecan) in tumors and normal human breast tissue was investigated. Multiplex RT-PCR data revealed different expression changes for different proteoglycans in human breast tumors--syndecan expression was activated compared to almost no expression in normal breast tissue, expression of decorin and lumican decreased 2-5- and 2-3-fold, respectively, and aggrecan transcription seems to be unaffected. A change of expression level of decorin correlated with expression of D-glucuronyl-C5-epimerase, a key enzyme responsible for the biosynthesis of idurone-containing glycosaminoglycans, possessing antimitotic activity. The results suggest that changes in decorin, lumican, and syndecan-1 expression in tumor tissue could induce a distortion of proteoglycan composition and mitotic activity of cells in human breast tumor. PMID:17922662

Eshchenko, T Yu; Rykova, V I; Chernakov, A E; Sidorov, S V; Grigorieva, E V

2007-09-01

215

Gene expression patterns in the human breast after pregnancy.  

PubMed

Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and whether such changes are transient or persistent. We examined the expression of a customized gene set in normal breast tissue from nulliparous, recently pregnant (0-2 years since pregnancy), and distantly pregnant (5-10 years since pregnancy) age-matched premenopausal women. This gene set included breast cancer biomarkers and genes related to immune/inflammation, extracellular matrix remodeling, angiogenesis, and hormone signaling. Laser capture microdissection and RNA extraction were done from formalin-fixed paraffin-embedded reduction mammoplasty and benign biopsy specimens and analyzed using real-time PCR arrays containing 59 pathway-specific and 5 housekeeping genes. We report 14 of 64 (22%) of the selected gene set to be differentially regulated (at P < 0.05 level) in nulliparous versus parous breast tissues. Based on gene set analysis, inflammation-associated genes were significantly upregulated as a group in both parous groups compared with nulliparous women (P = 0.03). Moreover, parous subjects had significantly reduced expression of estrogen receptor alpha (ERalpha, ESR1), progesterone receptor (PGR), and ERBB2 (Her2/neu) and 2-fold higher estrogen receptor-beta (ESR2) expression compared with nulliparous subjects. These initial data, among the first on gene expression in samples of normal human breast, provide intriguing clues about the mechanisms behind the time-dependent effects of pregnancy on breast cancer risk. PMID:20179293

Asztalos, Szilard; Gann, Peter H; Hayes, Meghan K; Nonn, Larisa; Beam, Craig A; Dai, Yang; Wiley, Elizabeth L; Tonetti, Debra A

2010-02-23

216

Effect of COX-2 Inhibitors on the Aromatase Gene Expression in Human Breast Cancer.  

National Technical Information Service (NTIS)

Aromatase (CYP-19) is responsible for estrogen biosynthesis within breast tumor tissue. Aromatase and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancer, and increased levels of prostaglandin (PG) activates the CYP19 promotor and incre...

C. L. Shapiro W. Burak R. Brueggemeier

2003-01-01

217

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer  

Microsoft Academic Search

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues.

C Zammit; R Coope; J J Gomm; S Shousha; C L Johnston; R C Coombes

2002-01-01

218

Methylation status of the Ep-CAM promoter region in human breast cancer cell lines and breast cancer tissue  

Microsoft Academic Search

We examined the methylation status of the Ep-CAM promoter region of human breast cancer cell lines and breast cancer tissue using MethyLight technology and bisulfite sequencing. We found the promoter of Ep-CAM-negative breast cancer cell lines Hs 578T to be methylated to a higher degree as compared to positive cell lines MCF-7. Demethylation of cell lines was performed using 5-aza-2?-deoxycytidine.

Gilbert Spizzo; Guenther Gastl; Peter Obrist; Dominic Fong; Margot Haun; Kurt Grünewald; Walther Parson; Cordula Eichmann; Simone Millinger; Heidi Fiegl; Raimund Margreiter; Albert Amberger

2007-01-01

219

Salinomycin Induces Autophagy in Colon and Breast Cancer Cells with Concomitant Generation of Reactive Oxygen Species  

PubMed Central

Background Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell death in human cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependent and independent cell death in colon cancer (SW480, SW620, RKO) and breast cancer cell lines (MCF-7, T47D, MDA-MB-453). Methodology/Principal Findings We detected features of apoptosis in all cell lines tested, but the executor caspases 3 and 7 were only strongly activated in RKO and MDA-MB-453 cells. MCF-7 and SW620 cells instead presented features of autophagy such as cytoplasmic vacuolization and LC3 processing. Caspase proficient cell lines activated autophagy at lower salinomycin concentrations and before the onset of caspase activation. Salinomycin also led to the formation of reactive oxygen species (ROS) eliciting JNK activation and induction of the transcription factor JUN. Salinomycin mediated cell death could be partially inhibited by the free radical scavenger N-acetyl-cysteine, implicating ROS formation in the mechanism of salinomycin toxicity. Conclusions Our data indicate that, in addition to its previously reported induction of caspase dependent apoptosis, the initiation of autophagy is an important and early effect of salinomycin in tumor cells.

Verdoodt, Berlinda; Vogt, Markus; Schmitz, Inge; Liffers, Sven-Thorsten; Tannapfel, Andrea; Mirmohammadsadegh, Alireza

2012-01-01

220

17?-Estradiol Enhances Breast Cancer Cell Motility and Invasion via Extra-Nuclear Activation of Actin-Binding Protein Ezrin  

PubMed Central

Estrogen promotes breast cancer metastasis. However, the detailed mechanism remains largely unknown. The actin binding protein ezrin is a key component in tumor metastasis and its over-expression is positively correlated to the poor outcome of breast cancer. In this study, we investigate the effects of 17?-estradiol (E2) on the activation of ezrin and its role in estrogen-dependent breast cancer cell movement. In T47-D breast cancer cells, E2 rapidly enhances ezrin phosphorylation at Thr567 in a time- and concentration-dependent manner. The signalling cascade implicated in this action involves estrogen receptor (ER) interaction with the non-receptor tyrosine kinase c-Src, which activates the phosphatidylinositol-3 kinase/Akt pathway and the small GTPase RhoA/Rho-associated kinase (ROCK-2) complex. E2 enhances the horizontal cell migration and invasion of T47-D breast cancer cells in three-dimensional matrices, which is reversed by transfection of cells with specific ezrin siRNAs. In conclusion, E2 promotes breast cancer cell movement and invasion by the activation of ezrin. These results provide novel insights into the effects of estrogen on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers.

Zhou, Kewen; Zhang, Chengxi; Xiang, Qiuling; Tan, Zhi; Wang, Tinghuai; Fu, Xiaodong

2011-01-01

221

Characterization of Novel Breast Cancer Specific Gene, BCSG1, in Human Breast Cancer Progression (97Breast).  

National Technical Information Service (NTIS)

We recently identified and cloned a novel breast cancer-specific gene BCSGl by direct differential cDNA sequencing. BCSG1 has a great sequence homology with Alzheimer disease (AD)-related neurotic protein synuclein, and thus was also named as synuclein ga...

Y. Liu

1999-01-01

222

IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines  

PubMed Central

Introduction IL-17 plays an important role in autoimmunity, promoting autoimmunity, inflammation and invasion in multiple sclerosis, rheumatoid arthritis and type I diabetes. The role of IL-17 in cancer is unclear, however, as there are few studies examining IL-17 protein expression in cancer. We therefore examined IL-17 protein expression in human breast cancer and modelled its potential biological significance in vitro. Methods Immunohistochemistry was used to determine IL-17 expression in breast cancers. Matrigel invasion assays were employed to examine the effect of IL-17 on cancer cell invasion by a panel of breast cancer cell lines. The role of matrix metalloproteinases (MMPs) was investigated with selective antagonists and immunoassays for MMP-2, MMP-3, MMP-9 and tissue inhibitor of MMP. Results IL-17-expressing cells with macrophage morphology were identified in the peritumoural area of a proportion of patients (8/19 patients). Macrophages were confirmed by CD68 staining on serial sections. With the exception of occasional lymphocytes, one patient with rare multinucleate giant cells and one patient with occasional expression of IL-17 in tumour cells, no other IL-17-positive cells were detected. Addition of IL-17 to cell lines in vitro stimulated marked invasion of Matrigel. In contrast, IL-17 did not promote the invasion of MCF7 or T47D cell lines. Invasion was initially thought to be dependent on MMPs, as evidenced by the broad-spectrum MMP inhibitor GM6001 and selective antagonists of MMP-2/MMP-9 and MMP-3. Measurement of MMP-2, MMP-3 and MMP-9, and tissue inhibitor of MMP 1 secretion, failed to reveal any changes in expression following IL-17 exposure. In contrast, TNF promoted secretion of MMPs but IL-17 did not augment TNF, indicating that IL-17 acts via an independent mechanism. Conclusions The present study is the first to describe in situ expression of IL-17 protein in human breast tumours and to propose a direct association between IL-17 and breast cancer invasion. The precise effectors of IL-17-dependent invasion remain to be characterised but could include a range of proteases such as a disintegrin and metalloproteinase protein or astacins. Nevertheless, this work identifies a novel potential mechanism for breast cancer invasion and tumour progression, the prognostic implication of which is currently under investigation.

Zhu, XingWu; Mulcahy, Lori A; Mohammed, Rabab AA; Lee, Andrew HS; Franks, Hester A; Kilpatrick, Laura; Yilmazer, Acelya; Paish, E Claire; Ellis, Ian O; Patel, Poulam M; Jackson, Andrew M

2008-01-01

223

Mammaglobin and Lipophilin Related Molecules in Normal and Tumor Human Breast Tissue: Expression, Hormone Regulation and Functional Analysis.  

National Technical Information Service (NTIS)

Genes, expression of which is breast specific or is altered during breast tumorigenesis, represent potential targets for new preventive and curative strategies. Such genes, Mammaglobin (MGBl), hSBEM (Human Small Breast Epithelial Mucin), Psoriasin, Estrog...

E. R. Leygue

2003-01-01

224

Mammaglobin and Lipophilin Related Molecules in Normal and Tumor Human Breast Tissue: Expression Hormone Regulation and Functional Analysis.  

National Technical Information Service (NTIS)

Genes, expression of which is breast specific or is altered during breast tumorigenesis, represent potential targets for new preventive and curative strategies. Such genes, Mammaglobin (MGB1), hSBEM (Human Small Breast Epithelial Mucin), Psoriasin, Estrog...

E. R. Leygue

2004-01-01

225

Discovery of estrogen receptor ? target genes and response elements in breast tumor cells  

Microsoft Academic Search

Background: Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. Results: Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells,

Chin-Yo Lin; Anders Ström; Vinsensius Berlian Vega; Say Li Kong; Ai Li Yeo; Jane S Thomsen; Wan Ching Chan; Balraj Doray; Dhinoth K Bangarusamy; Adaikalavan Ramasamy; Liza A Vergara; Suisheng Tang; Allen Chong; Vladimir B Bajic; Lance D Miller; Edison T Liu

2004-01-01

226

TGF?1 Inhibition Increases the Radiosensitivity of Breast Cancer Cells In Vitro and Promotes Tumor Control by Radiation In Vivo  

PubMed Central

Purpose To determine whether inhibition of TGF? signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo. Experimental Design TGF?-mediated growth and Smad phosphorylation of MCF7, Hs578T, MDA-MB-231, and T47D human breast cancer cell lines were examined and correlated with clonogenic survival following graded radiation doses with and without pretreatment with LY364947, a small molecule inhibitor of the TGF? type I receptor kinase. The DNA damage response was assessed in irradiated MDA-MB-231 cells pretreated with LY364947 in vitro and LY2109761, a pharmacokinetically stable inhibitor of TGF? signaling, in vivo. The in vitro response of a syngeneic murine tumor, 4T1, was tested using a TGF? neutralizing antibody, 1D11, with single or fractionated radiation doses in vivo. Results Human breast cancer cell lines pretreated with TGF? small molecule inhibitor were radio-sensitized, irrespective of sensitivity to TGF? growth inhibition. Consistent with increased clonogenic cell death, radiation-induced phosphorylation of H2AX and p53 was significantly reduced in MDA-MB-231 triple-negative breast cancer cells when pretreated in vitro or in vivo with a TGFfS type I receptor kinase inhibitor. Moreover, TGF? neutralizing antibodies increased radiation sensitivity, blocked ?H2AX foci formation, and significantly increased tumor growth delay in 4T1 murine mammary tumors in response to single and fractionated radiation exposures. Conclusion These results show that TGF? inhibition prior to radiation attenuated DNA damage responses, increased clonogenic cell death, and promoted tumor growth delay, and thus may be an effective adjunct in cancer radiotherapy.

Bouquet, Fanny; Pal, Anupama; Pilones, Karsten A.; Demaria, Sandra; Hann, Byron; Akhurst, Rosemary J.; Babb, Jim S.; Lonning, Scott M.; DeWyngaert, J. Keith; Formenti, Silvia C.; Barcellos-Hoff, Mary Helen

2013-01-01

227

Anticomplement activities of human breast-milk  

Microsoft Academic Search

Objective and Design: It has long been observed that the human milk possesses significant anti-inflammatory properties, while simultaneously protecting the infant against many intestinal and respiratory pathogens. There is, however, a paucity of information on the degree and extent of this anti-inflammatory activity. In the present study, the inhibitory effects of different fractions of human milk on serum complement activity

M. O. Ogundele

1999-01-01

228

Plasminogen Activator Activity and Composition in Human Breast Cancer1  

Microsoft Academic Search

The plasminogen activator activity of human breast tumors was determined quantitatively in extracts of 33 primary tumors, 11 lymph node métastases,and 11 normal tissues. Activities varied more widely in the neoplastic tissues than in the normal ones. The mean activator content of the tumors (primary and metastasis) was significantly higher (p < 0.01) than that of normal tissues: 4.4-fold on

John L. Evers; Jashbhai Patel; Judith M. Madeja; Sarah L. Schneider; Grant H. Hobika; Sarah M. Camiolo

229

Human Breast Milk and Xenoestrogen Exposure: A Possible Impact on Human Health  

Microsoft Academic Search

Human milk is the best natural and optimal food for neonates with several immunologic, developmental and practical advantages throughout childhood. Although the World Health Organization strongly supports breastfeeding, it recognizes the potential health risks posed by the presence of environmental toxicants in breast milk. Contamination of human milk is widespread and due to decades of inadequately controlled pollution by toxicants,

Francesco Massart; Joshua Chuck Harrell; Giovanni Federico; Giuseppe Saggese

2005-01-01

230

Detection of human papillomavirus DNA in breast cancer of patients with cervical cancer history  

Microsoft Academic Search

Background: Recent studies have revealed a possible role for the human papillomavirus (HPV) in the pathogenesis of breast cancer. In this study, patients having both a history of invasive cervical cancer and breast cancer as second primary cancer were selected for enrolment in a study of breast carcinomas for the presence of HPV. Methods: Paraffin-embedded tissue from cervical cancer, pelvic

Andreas Widschwendter; Thomas Brunhuber; Annemarie Wiedemair; Elisabeth Mueller-Holzner; Christian Marth

2004-01-01

231

Involvement of Ras Activation in Human Breast Cancer Cell Signaling, Invasion, and Anoikis  

Microsoft Academic Search

Although mutated forms of ras are not associated with the majority of breast cancers (<5%), there is considerable experimental evidence that hyperactive Ras can promote breast cancer growth and development. Therefore, we determined whether Ras and Ras-responsive signaling pathways were activated persistently in nine widely studied human breast cancer cell lines. Although only two of the lines harbor mutationally activated

Lynn B. Eckert; Gretchen A. Repasky; Aylin S. Ulku; Aidan McFall; Hong Zhou; Carolyn I. Sartor; Channing J. Der

2004-01-01

232

Detection of human mammary tumor virus proteins in human breast cancer cells.  

PubMed

Mouse mammary tumor virus (MMTV) has been proven to induce mammary cancer in mice. MMTV-like env gene sequences have been detected in one-third of the human breast tumors studied. The whole proviral structure with 95% homology to MMTV was found in two human breast tumors and was designated as human mammary tumor virus (HMTV). HMTV viral particles with betaretroviral features have been isolated. In addition, a retrovirus called human betaretrovirus (HBRV), homologous to the mentioned retroviruses, has been isolated from tissues of patients with primary biliary cirrhosis. In this report, the expression of HMTV envelope (Env) and capsid (Ca) was detected in 10 primary cultures of human breast cancer containing HMTV sequences (MSSM) by Western blot and fluorescence activated cell sorting (FACS), using a panel of antibodies against HMTV Env, HBRV Env and Ca and the MMTV Env Gp36 and Ca P27 proteins. By contrast, HMTV proteins did not react with antibody against the MMTV Env Gp52 protein. All the antibodies detected MMTV proteins with exception of two out of four monoclonal antibodies against HMTV Env. Approximately 13% of the MSSM cells showed HMTV protein expression by FACS analysis. This report shows the expression of HMTV proteins for the first time in human breast cancer cells using a panel of antibodies against HMTV, HBRV and MMTV proteins. This should be taken into consideration when MMTV antibodies are used to detect HMTV proteins in human tissues. PMID:19781575

Melana, Stella M; Nepomnaschy, Irene; Hasa, Jennifer; Djougarian, Alina; Djougarian, Anna; Holland, James F; Pogo, Beatriz G T

2009-09-23

233

Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells  

Microsoft Academic Search

Metastatic breast cancer cells exhibit the selective ability to seed and grow in the skeleton. We and others have previously\\u000a reported that human breast tumors which metastasize to the skeleton overexpress bone matrix extracellular proteins. In an\\u000a attempt to reveal the osteoblast-like phenotype of osteotropic breast cancer cells, we performed a microarray study on a model\\u000a of breast cancer bone

A. Bellahcène; R. Bachelier; C. Detry; R. Lidereau; P. Clézardin; V. Castronovo

2007-01-01

234

Concentrations of parabens in human breast tumours  

Microsoft Academic Search

Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term,

P. D. Darbre; A. Aljarrah; W. R. Miller; N. G. Coldham; M. J. Sauer; G. S. Pope

2004-01-01

235

Gene expression profiles of human breast cancer progression  

PubMed Central

Although distinct pathological stages of breast cancer have been described, the molecular differences among these stages are largely unknown. Here, through the combined use of laser capture microdissection and DNA microarrays, we have generated in situ gene expression profiles of the premalignant, preinvasive, and invasive stages of human breast cancer. Our data reveal extensive similarities at the transcriptome level among the distinct stages of progression and suggest that gene expression alterations conferring the potential for invasive growth are already present in the preinvasive stages. In contrast to tumor stage, different tumor grades are associated with distinct gene expression signatures. Furthermore, a subset of genes associated with high tumor grade is quantitatively correlated with the transition from preinvasive to invasive growth.

Ma, Xiao-Jun; Salunga, Ranelle; Tuggle, J. Todd; Gaudet, Justin; Enright, Edward; McQuary, Philip; Payette, Terry; Pistone, Maria; Stecker, Kimberly; Zhang, Brian M.; Zhou, Yi-Xiong; Varnholt, Heike; Smith, Barbara; Gadd, Michelle; Chatfield, Erica; Kessler, Jessica; Baer, Thomas M.; Erlander, Mark G.; Sgroi, Dennis C.

2003-01-01

236

Metalloproteinases in Human Invasive Breast Carcinomas  

Microsoft Academic Search

Activation of the zymogen of matrix metalloprotelnase 2 (proMMP-2, progelatinase A) possibly is one ofthe key steps In Invasion and metastasis of varioushumancarcinomas. Threedifferentmembrane-type MMPS (MT-MMPs), MT1., MT2-, and MT3-MMPSare thought to be activators of proMMP-2 Inthetissues.MT4.MMP Isstructurally differentfromthe other three enzymes, sad Its function as proMMP-2 activator is uncertain. Inthepresentstudyof humanInvasive breastcarcinomas, weexamined a correlation between the expression of

Hirohisa Ueno; Hiroyuki Nakamura; Masaki Inoue; Kazushi Imai; Masakuni Noguchi; Hiroshi Sato; Motoharu Seiki; Yasunori Okada

237

Acetonic Extract of Buxus sempervirens Induces Cell Cycle Arrest, Apoptosis and Autophagy in Breast Cancer Cells  

PubMed Central

Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC50 ranging from 7.74 µg/ml to 12.5 µg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC50 of 19.24 µg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC50 did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer.

Ait-Mohamed, Ouardia; Battisti, Valentine; Joliot, Veronique; Fritsch, Lauriane; Pontis, Julien; Medjkane, Souhila; Redeuilh, Catherine; Lamouri, Aazdine; Fahy, Christine; Rholam, Mohamed; Atmani, Djebbar; Ait-Si-Ali, Slimane

2011-01-01

238

Endocrine disruptors fludioxonil and fenhexamid stimulate miR-21 expression in breast cancer cells.  

PubMed

Fenhexamid and fludioxonil are antifungal agents used in agricultural applications, which are present at measurable amounts in fruits and vegetables. Fenhexamid and fludioxonil showed endocrine disruptor activity as antiandrogens in an androgen receptor reporter assay in engineered human breast cancer cells. Little is known about how environmental chemicals regulate microRNA (miRNA) expression. This study examined the effect of fenhexamid and fludioxonil on the expression of the oncomiR miR-21 in MCF-7, T47D, and MDA-MB-231 human breast cancer cells and downstream targets of miR-21 in MCF-7 cells. Fenhexamid and fludioxonil stimulated miR-21 expression in a concentration-dependent manner and reduced the expression of miR-21 target Pdcd4 protein. Antisense to miR-21 blocked the increase in Pdcd4 protein by fenhexamid and fludioxonil. Fenhexamid and fludioxonil reduced miR-125b and miR-181a, demonstrating specificity of miRNA regulation. Induction of miR-21 was inhibited by the estrogen receptor antagonist fulvestrant, by androgen receptor antagonist bicalutamide, by actinomycin D and cycloheximide, and by inhibitors of the mitogen-activated protein kinases and phosphoinositide 3-kinase pathways. Fenhexamid activation was inhibited by the arylhydrocarbon receptor antagonist ?-napthoflavone. Fenhexamid and fludioxonil did not affect dihydrotestosterone-induced miR-21 expression. Fludioxonil, but not fenhexamid, inhibited MCF-7 cell viability, and both inhibited estradiol-induced cell proliferation and reduced cell motility. Together these data indicate that fenhexamid and fludioxonil use similar and distinct mechanisms to increase miR-21 expression with downstream antiestrogenic activity. PMID:23052036

Teng, Yun; Manavalan, Tissa T; Hu, Chuan; Medjakovic, Svjetlana; Jungbauer, Alois; Klinge, Carolyn M

2012-10-10

239

Silibinin inhibits Wnt/?-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells.  

PubMed

Silibinin is a natural compound isolated from milk thistle seed extracts, and has traditionally been used as a hepatoprotectant. A number of studies have also established the cancer therapeutic and chemopreventive role of silibinin in both in vitro and in vivo models. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for the Wnt/?-catenin pathway and represents a promising target for cancer prevention and therapy. In the present study, we found that silibinin was able to repress endogenous LRP6 expression and block Wnt3A-induced LRP6 phosphorylation and Wnt/?-catenin signaling activation in HEK293 cells. Importantly, silibinin was also able to suppress endogenous LRP6 expression and phosphorylation and block Wnt/?-catenin signaling in prostate cancer PC-3 and DU-145 cells and breast cancer MDA-MB-231 and T-47D cells. Mechanistically, silibinin inhibited LRP6 promoter activity and decreased LRP6 mRNA levels in prostate and breast cancer cells. Finally, we demonstrated that silibinin displayed anticancer activity with IC(50) values comparable to those shown to suppress LRP6 expression and Wnt/?-catenin signaling activities in prostate and breast cancer cells. Our data indicate that silibinin is a novel small molecule Wnt/?-catenin signaling inhibitor by suppressing Wnt co-receptor LRP6 expression at the transcription level, and that the anti-cancer activity of silibinin is associated with its inhibitory effect on Wnt/LRP6 signaling. PMID:22820499

Lu, Wenyan; Lin, Cuihong; King, Taj D; Chen, Honghong; Reynolds, Robert C; Li, Yonghe

2012-07-20

240

Expression of keratinocyte growth factor and its receptor in human breast cancer  

Microsoft Academic Search

The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) procedure. We found similar levels of KGF

GS Bansal; HC Cox; S Marsh; JJ Gomm; C Yiangou; Y Luqmani; RC Coombes; CL Johnston

1997-01-01

241

A humanized anti-osteopontin antibody inhibits breast cancer growth and metastasis in vivo  

Microsoft Academic Search

Osteopontin (OPN) has been implicated as an important mediator of breast cancer progression and metastasis and has been investigated\\u000a for use as a potential therapeutic target in the treatment of breast cancer. However, the in vivo antitumor effect of anti-OPN\\u000a antibodies on breast cancer has not been reported. In this study, a mouse anti-human OPN antibody (1A12) was humanized by

Jianxin Dai; Bohua Li; Jinping Shi; Ling Peng; Dapeng Zhang; Weizhu Qian; Sheng Hou; Lei Zhao; Jie Gao; Zhiguo Cao; Jian Zhao; Hao Wang; Yajun Guo

2010-01-01

242

Angiotensin II type 1 receptor expression in human breast tissues.  

PubMed Central

We demonstrate the expression of angiotensin II type 1 (AT1) receptors in normal and diseased human breast tissues. Using monoclonal antibody 6313/G2, directed against a specific sequence in the extracellular domain of the AT1 receptor, immunocytochemical analysis revealed positive immunoreactivity in membrane and cytoplasm of specific cell types. Immunoblotting of solubilized proteins separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) from benign and malignant tumours identified a single immunoreactive species with a molecular mass of approximately 60 kDa, consistent with that of the mature glycosylated receptor. In studies of [125I]angiotensin II binding using breast membrane preparations, concentrations of specific angiotensin II binding sites were found to range from 1.8 to 100 fmol mg(-1) protein, with a K(d) of approximately 60 nM. Most of the specifically bound [125I]angiotensin II was displaced by losartan, a specific angiotensin II type 1 receptor antagonist, while less was displaced by the AT2 receptor type antagonist, CGP42112A, thus confirming the prevalence of AT1 receptors in this tissue type. These data suggest that the renin-angiotensin system may be involved in normal and abnormal breast tissue function. Images Figure 1 Figure 4

Inwang, E. R.; Puddefoot, J. R.; Brown, C. L.; Goode, A. W.; Marsigliante, S.; Ho, M. M.; Payne, J. G.; Vinson, G. P.

1997-01-01

243

Marker evaluation of human breast and bladder cancers  

SciTech Connect

We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. (California Univ., San Francisco, CA (USA))

1990-11-02

244

Construction of an MUC-1 promoter driven, conditionally replicating adenovirus that expresses the sodium iodide symporter for gene therapy of breast cancer  

PubMed Central

Introduction The sodium iodide symporter (NIS) directs the uptake and concentration of iodide in thyroid cells. This in turn allows radioiodine imaging and therapy for thyroid cancer. To extend the use of NIS-mediated radioiodine therapy to other types of cancer, we successfully transferred and expressed the sodium-iodide symporter (NIS) gene in prostate, colon, and breast cancer cells both in vivo and in vitro by using non-replicating adenoviral vectors. Methods To improve virotherapy efficiency, we developed a conditionally replicating adenovirus (CRAd) in which the transcriptional cassette RSV promoter-human NIScDNA-bGH polyA was also inserted at the E3 region. The E1a gene is driven by the tumor-specific promoter MUC-1 in the CRAd Ad5AMUCH_RSV-NIS. Results In vitro infection of the MUC-1-positive breast cell line T47D resulted in virus replication, cytolysis, and release of infective viral particles. Conversely, the MUC-1-negative breast cancer cell line MDA-MB-231 was refractory to the viral cytopathic effect and did not support viral replication. The data indicate that Ad5AMUCH_RSV-NIS activity is stringently restricted to MUC-1-positive cancer cells. Radioiodine uptake was readily measurable in T47 cells infected with Ad5AMUCH_RSV-NIS 24 hours after infection, thus confirming NIS expression before viral-induced cell death. Conclusions This construct may allow multimodal therapy, combining virotherapy with radioiodine therapy to be developed as a novel treatment for breast and other MUC1-overexpressing cancers.

Trujillo, Miguel A; Oneal, Michael J; Davydova, Julia; Bergert, Elizabeth; Yamamoto, Masato; Morris, John C

2009-01-01

245

BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells  

PubMed Central

Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals derived from cruciferous vegetables and soy, respectively, with potential cancer prevention activity for hormone-responsive tumours (e.g., breast and prostate cancers). Previously, we showed that I3C induces BRCA1 expression and that both I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen receptor (ER-?) activity in human breast cancer cells. We now report that both I3C and genistein induce the expression of both breast cancer susceptibility genes (BRCA1 and BRCA2) in breast (MCF-7 and T47D) and prostate (DU-145 and LNCaP) cancer cell types, in a time- and dose-dependent fashion. Induction of the BRCA genes occurred at low doses of I3C (20??M) and genistein (0.5–1.0??M), suggesting potential relevance to cancer prevention. A combination of I3C and genistein gave greater than expected induction of BRCA expression. Studies using small interfering RNAs (siRNAs) and BRCA expression vectors suggest that the phytochemical induction of BRCA2 is due, in part, to BRCA1. Functional studies suggest that I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2. Inhibition of E2-stimulated ER-? activity by I3C and genistein was dependent upon BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by I3C and genistein was partially reversed by BRCA1-siRNA. Finally, we provide evidence suggesting that the phytochemical induction of BRCA1 expression is due, in part, to endoplasmic reticulum stress response signalling. These findings suggest that the BRCA genes are molecular targets for some of the activities of I3C and genistein.

Fan, S; Meng, Q; Auborn, K; Carter, T; Rosen, E M

2006-01-01

246

Correlation of Lactogenic Receptor Concentration in Human Breast Cancer with Estrogen Receptor Concentration  

Microsoft Academic Search

The presence of receptors for lactogenic hormones in human breast cancer tissue has been documented previously, but the relationship between the expression of these receptors and estrogen receptor (ER) status has not been adequately studied. In this report, the specificity of 125l-humangrowth hormone (HGH) binding in both cultured human breast cancer cell lines and tumor biopsies was studied to establish

Liam J. Murphy; Leigh C. Murphy; Elizabeth Vrhovsek; Robert L. Sutherland; Leslie Lazarus

247

Estrogenic effects of phenolphthalein on human breast cancer cells in vitro  

Microsoft Academic Search

Summary There is a structural similarity between phenolphthalein and the triphenylethylenes which are known to interact with the estrogen receptor of human breast tissue. Phenolphthalein (10 µM) competed with estrogen for binding to MCF-7 human breast cancer cells in tissue culture and induced the synthesis of the progesterone receptor. The antiestrogen 4-hydroxytamoxifen blocked progesterone receptor induction both by estradiol and

Peter Marcus Ravdin; Marc van Beurden; V. Craig Jordan

1987-01-01

248

American Ginseng in the Prevention and Treatment of Human Breast Cancer.  

National Technical Information Service (NTIS)

This study is examining the effects of American ginseng on human breast cancer cell proliferation in vitro and in vivo. An extract of American ginseng was shown to significantly decrease MCF-7 and MDA-MB-231 human breast cancer cell proliferation in vitro...

L. Murphy

2000-01-01

249

Isolation of Estrogen-Responsive Genes in Human Breast Cancer Cells.  

National Technical Information Service (NTIS)

The purpose of this proposal is to isolate and identify estrogen- responsive genes in human breast cancer cells using the chromatin immunoprecipitation (ChIP) protocol. Estrogen receptor (ER) -bound DNA has been isolated using ChIP from human breast cance...

J. R. Davie

2002-01-01

250

Specific cytoplasmic alpha-fetoprotein binding protein in MCF7 human breast cancer cells and primary breast cancer tissue  

Microsoft Academic Search

Summary Direct evidence was obtained for the existence of a specific high affinity alpha-fetoprotein (AFP)-binding protein in the cytosol of both MCF-7 human breast cancer cultured cells and primary breast cancer tissue from postmenopausal women using a nitrocellulose blotting assay. Scatchard analysis of the binding data for MCF-7 cells at 37° C revealed the presence of a single class of

William Biddle; Edward J. Sarcione

1987-01-01

251

Genetically Targeted Radiotherapy Utilizing the Human Sodium Iodide Symporter in Human Breast Carcinoma Cells.  

National Technical Information Service (NTIS)

The purpose of this proposal was to examine the efficiency of NIS mediated genetically targeted radiotherapy as a possible non-invasive therapeutic treatment in human breast carcinoma. SK-Br-3 cells were transfected with hNlS plasmid to develop stable NIS...

K. Krager F. E. Domann

2006-01-01

252

Genetically Targeted Radiotherapy Utilizing the Human Sodium Iodide Symporter in Human Breast Carcinoma Cells.  

National Technical Information Service (NTIS)

The purpose of this proposal was to elaborate on the viability of NIS-mediated genetically targeted radiotherapy as a possible novel therapeutic intervention in human breast carcinoma. Problems encountered with SK- Pr-3 forced other cell limes to be utili...

K. Krager

2007-01-01

253

Bisphenol A at Low Nanomolar Doses Confers Chemoresistance in Estrogen Receptor-?-Positive and -Negative Breast Cancer Cells  

PubMed Central

Background Resistance to chemotherapy is a major problem facing breast cancer patients, and identifying potential contributors to chemoresistance is a critical area of research. Bisphenol A (BPA) has long been suspected to promote carcinogenesis, but the high doses of BPA used in many studies generated conflicting results. In addition, the mechanism by which BPA exerts its biological actions is unclear. Although estrogen has been shown to antagonize anticancer drugs, the role of BPA in chemoresistance has not been examined. Objective The objective of our study was to determine whether BPA at low nanomolar concentrations opposes the action of doxorubicin, cisplatin, and vinblastine in the estrogen receptor-? (ER?)-positive T47D and the ER?-negative MDA-MB-468 breast cancer cells. Methods We determined the responsiveness of cells to anticancer drugs and BPA using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay. Specific ER? and ER? inhibitors and real-time polymerase chain reaction were used to identify potential receptor(s) that mediate the actions of BPA. Expression of antiapoptotic proteins was assessed by Western blotting. Results BPA antagonizes the cytotoxicity of multiple chemotherapeutic agents in both ER?-positive and -negative breast cancer cells independent of the classical ERs. Both cell types express alternative ERs, including G-protein–coupled receptor 30 (GPR30) and members of the estrogen-related receptor family. Increased expression of antiapoptotic proteins is a potential mechanism by which BPA exerts its anticytotoxic effects. Conclusions BPA at environmentally relevant doses reduces the efficacy of chemotherapeutic agents. These data provide considerable support to the accumulating evidence that BPA is hazardous to human health.

LaPensee, Elizabeth W.; Tuttle, Traci R.; Fox, Sejal R.; Ben-Jonathan, Nira

2009-01-01

254

Development of Ligand-Transformed Alpha-Fetoprotein for Use Against Breast Cancer in Humans.  

National Technical Information Service (NTIS)

During the first two years of this project, we established that nanogram quantities of ligand- activated and microgram quantities of unactivated natural and recombinant human AFP inhibited growth of estrogen-dependent MCF-7 human breast cancer. During yea...

J. A. Bennett

1997-01-01

255

Novel Angiogenic Domains: Use in Identifying Unique Transforming and Tumor Promoting Pathways in Human Breast Cancer.  

National Technical Information Service (NTIS)

Breast cancers in humans often grow slowly or even remain undetectable for long periods of time only to reappear in discreet stages as progressively more malignant tumors. Recently studies in both human cancers and experimental cancers in animals have est...

T. F. Deuel

2004-01-01

256

Novel Angiogenic Domains: Use in Identifying Unique Transforming and Tumor Promoting Pathways in Human Breast Cancer.  

National Technical Information Service (NTIS)

Breast cancers in humans often grow slowly or even remain undetectable for long periods of time only to reappear in discreet stages as progressively more malignant tumors. Recently, studies in both human cancers and experimental cancers in animals have es...

T. F. Deuel

2003-01-01

257

PACAP (6–38) is a PACAP receptor antagonist for breast cancer cells  

Microsoft Academic Search

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. 125I–PACAP–27 bound with high affinity (Kd=5?nM) to T47D cells (Bmax?=?29,000 per cell). Specific 125I–PACAP–27 binding was inhibited half maximally by PACAP–27, PACAP–38, PACAP(6–38) and PACAP(28–38) with IC50 values of 8, 17, 750 and >3000?nM, respectively. By RT–PCR, PACAP receptor mRNA was present in MCF–7

Julius Leyton; Yehoshua Gozes; Joseph Pisegna; David Coy; Sally Purdom; Marchessini Casibang; Farah Zia; Terry W. Moody

1999-01-01

258

Analysis of a heterogeneous group of human breast carcinoma associated glycoproteins bearing the Tn determinant  

Microsoft Academic Search

The Tn determinant (GalNAca-O-Ser\\/Thr) is expressed by about 90% of human carcinomas, but is cryptic in most normal human tissues. A murine monoclonal antibody (MAb) 83D4, developed following immunization with human breast carcinoma cells, reacts with a Tn-related epitope. In the present study we characterized the glycoprotein antigen identified by 83D4 in the human breast carcinoma cell line MCF-7. We

Eduardo Osinaga; Gianfranco Pancino; Nicole Porchet; Nora Berois; Patricia De Cremoux; Dominique Mistro; Jean Pierre Aubert; Fabian Calvo; Alberto Roseto

1994-01-01

259

Expression of keratinocyte growth factor and its receptor in human breast cancer.  

PubMed

The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) procedure. We found similar levels of KGF mRNA in malignant and non-malignant breast tissues. The study of the amount of KGF mRNA in breast cell lines and purified populations of cells revealed that fibroblasts are the predominant source of KGF with malignant and non-malignant epithelial cells containing very low levels of KGF mRNA. We have examined the distribution of fibroblast growth factor receptor (FGFR)-2-IIIb, which is a high-affinity receptor for KGF and find that it is present on malignant and non-malignant epithelial cells. The level of FGFR-2-IIIb present on breast cancer cell lines was sufficient for KGF stimulation of breast cancer cell proliferation. Other members of the fibroblast growth factor family have been either not expressed in the human breast (FGF3, FGF4) or have been found at much reduced levels in breast cancer (FGF1, FGF2) and this is the first member of the family to potentially influence the progression of breast cancer through stimulation of cell division. PMID:9184170

Bansal, G S; Cox, H C; Marsh, S; Gomm, J J; Yiangou, C; Luqmani, Y; Coombes, R C; Johnston, C L

1997-01-01

260

Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells  

Microsoft Academic Search

Introduction  Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma\\u000a cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer\\u000a cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic\\u000a factor for poor survival in breast cancer

Yvonne Radestock; Cuong Hoang-Vu; Sabine Hombach-Klonisch

2008-01-01

261

S14 protein in breast cancer cells: Direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth  

SciTech Connect

Most breast cancers exhibit brisk lipogenesis, and require it for growth. S14 is a lipogenesis-related nuclear protein that is overexpressed in most breast cancers. Sterol response element-binding protein-1c (SREBP-1c) is required for induction of lipogenesis-related genes, including S14 and fatty acid synthase (FAS), in hepatocytes, and correlation of SREBP-1c and FAS expression suggested that SREBP-1c drives lipogenesis in tumors as well. We directly tested the hypothesis that SREBP-1c drives S14 expression and mediates lipogenic effects of progestin in T47D breast cancer cells. Dominant-negative SREBP-1c inhibited induction of S14 and FAS mRNAs by progestin, while active SREBP-1c induced without hormone and superinduced in its presence. Changes in S14 mRNA were reflected in protein levels. A lag time and lack of progestin response elements indicated that S14 and FAS gene activation by progestin is indirect. Knockdown of S14 reduced, whereas overexpression stimulated, T47D cell growth, while nonlipogenic MCF10a mammary epithelial cells were not growth-inhibited. These data directly demonstrate that SREBP-1c drives S14 gene expression in breast cancer cells, and progestin magnifies that effect via an indirect mechanism. This supports the prediction, based on S14 gene amplification and overexpression in breast tumors, that S14 augments breast cancer cell growth and survival.

Martel, Peter M. [Department of Medicine, Division of Endocrinology, Dartmouth Medical School (United States); Norris Cotton Cancer Center, Dartmouth Medical School (United States); Bingham, Chad M. [Department of Medicine, Division of Endocrinology, Dartmouth Medical School (United States); Norris Cotton Cancer Center, Dartmouth Medical School (United States); McGraw, Charles J. [Department of Medicine, Division of Endocrinology, Dartmouth Medical School (United States); Norris Cotton Cancer Center, Dartmouth Medical School (United States); Baker, Christina L. [Department of Medicine, Division of Endocrinology, Dartmouth Medical School (United States); Norris Cotton Cancer Center, Dartmouth Medical School (United States); Morganelli, Peter M. [Department of Microbiology and Immunology, Dartmouth Medical School (United States); Norris Cotton Cancer Center, Dartmouth Medical School (United States); Meng, Marie Louise [Department of Medicine, Division of Endocrinology, Dartmouth Medical School (United States); Norris Cotton Cancer Center, Dartmouth Medical School (United States); Armstrong, Jessica M. [Norris Cotton Cancer Center, Dartmouth Medical School (United States); Department of Physiology, Dartmouth Medical School (United States); Moncur, Joel T. [Department of Medicine, Division of Endocrinology, Dartmouth Medical School (United States); Kinlaw, William B. [Department of Medicine, Division of Endocrinology, Dartmouth Medical School (United States) and Norris Cotton Cancer Center, Dartmouth Medical School (United States)]. E-mail: william.kinlaw@hitchcock.org

2006-02-01

262

Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis.  

PubMed

BACKGROUND Secretory GTPases like Rab27B control vesicle exocytosis and deliver critical proinvasive growth regulators into the tumor microenvironment. The expression and role of Rab27B in breast cancer were unknown. METHODS Expression of green fluorescent protein (GFP) fused with wild-type Rab3D, Rab27A, or Rab27B, or Rab27B point mutants defective in GTP/GDP binding or geranylgeranylation, or transient silencing RNA to the same proteins was used to study Rab27B in estrogen receptor (ER)-positive human breast cancer cell lines (MCF-7, T47D, and ZR75.1). Cell cycle progression was evaluated by flow cytometry, western blotting, and measurement of cell proliferation rates, and invasion was assessed using Matrigel and native type I collagen substrates. Orthotopic tumor growth, local invasion, and metastasis were analyzed in mouse xenograft models. Mass spectrometry identified proinvasive growth regulators that were secreted in the presence of Rab27B. Rab27B protein levels were evaluated by immunohistochemistry in 59 clinical breast cancer specimens, and Rab3D, Rab27A, and Rab27B mRNA levels were analyzed by quantitative real-time polymerase chain reaction in 20 specimens. Statistical tests were two-sided. RESULTS Increased expression of Rab27B promoted G(1) to S phase cell cycle transition, proliferation and invasiveness of cells in culture, and invasive tumor growth and hemorrhagic ascites production in a xenograft mouse model (n = 10; at 10 weeks, survival of MCF-7 GFP- vs GFP-Rab27B-injected mice was 100% vs 62.5%, hazard ratio = 0.26, 95% confidence interval = 0.08 to 0.88, P = .03). Mass spectrometric analysis of purified Rab27B-secretory vesicles identified heat-shock protein 90alpha as key proinvasive growth regulator. Heat-shock protein 90alpha secretion was Rab27B-dependent and was required for matrix metalloproteinase-2 activation. All Rab27B-mediated functional responses were GTP- and geranylgeranyl-dependent. Presence of endogenous Rab27B mRNA and protein, but not of Rab3D or Rab27A mRNA, was associated with lymph node metastasis (P < .001) and differentiation grade (P = .001) in ER-positive human breast tumors. CONCLUSIONS Rab27B regulates invasive growth and metastasis in ER-positive breast cancer cell lines, and increased expression is associated with poor prognosis in humans. PMID:20484105

Hendrix, An; Maynard, Dawn; Pauwels, Patrick; Braems, Geert; Denys, Hannelore; Van den Broecke, Rudy; Lambert, Jo; Van Belle, Simon; Cocquyt, Veronique; Gespach, Christian; Bracke, Marc; Seabra, Miguel C; Gahl, William A; De Wever, Olivier; Westbroek, Wendy

2010-05-18

263

Effect of the Secretory Small GTPase Rab27B on Breast Cancer Growth, Invasion, and Metastasis  

PubMed Central

Background Secretory GTPases like Rab27B control vesicle exocytosis and deliver critical proinvasive growth regulators into the tumor microenvironment. The expression and role of Rab27B in breast cancer were unknown. Methods Expression of green fluorescent protein (GFP) fused with wild-type Rab3D, Rab27A, or Rab27B, or Rab27B point mutants defective in GTP/GDP binding or geranylgeranylation, or transient silencing RNA to the same proteins was used to study Rab27B in estrogen receptor (ER)–positive human breast cancer cell lines (MCF-7, T47D, and ZR75.1). Cell cycle progression was evaluated by flow cytometry, western blotting, and measurement of cell proliferation rates, and invasion was assessed using Matrigel and native type I collagen substrates. Orthotopic tumor growth, local invasion, and metastasis were analyzed in mouse xenograft models. Mass spectrometry identified proinvasive growth regulators that were secreted in the presence of Rab27B. Rab27B protein levels were evaluated by immunohistochemistry in 59 clinical breast cancer specimens, and Rab3D, Rab27A, and Rab27B mRNA levels were analyzed by quantitative real-time polymerase chain reaction in 20 specimens. Statistical tests were two-sided. Results Increased expression of Rab27B promoted G1 to S phase cell cycle transition, proliferation and invasiveness of cells in culture, and invasive tumor growth and hemorrhagic ascites production in a xenograft mouse model (n = 10; at 10 weeks, survival of MCF-7 GFP- vs GFP-Rab27B–injected mice was 100% vs 62.5%, hazard ratio = 0.26, 95% confidence interval = 0.08 to 0.88, P = .03). Mass spectrometric analysis of purified Rab27B-secretory vesicles identified heat-shock protein 90? as key proinvasive growth regulator. Heat-shock protein 90? secretion was Rab27B-dependent and was required for matrix metalloproteinase-2 activation. All Rab27B-mediated functional responses were GTP- and geranylgeranyl-dependent. Presence of endogenous Rab27B mRNA and protein, but not of Rab3D or Rab27A mRNA, was associated with lymph node metastasis (P < .001) and differentiation grade (P = .001) in ER-positive human breast tumors. Conclusions Rab27B regulates invasive growth and metastasis in ER-positive breast cancer cell lines, and increased expression is associated with poor prognosis in humans.

Hendrix, An; Maynard, Dawn; Pauwels, Patrick; Braems, Geert; Denys, Hannelore; Van den Broecke, Rudy; Lambert, Jo; Van Belle, Simon; Cocquyt, Veronique; Gespach, Christian; Bracke, Marc; Seabra, Miguel C.; Gahl, William A.

2010-01-01

264

Cytotoxic activity of 3,3?,4,4?,5,5?-hexahydroxystilbene against breast cancer cells is mediated by induction of p53 and downregulation of mitochondrial superoxide dismutase  

Microsoft Academic Search

The phytochemical resveratrol, which is found in grapes and red wine, has been reported to have a variety of biological properties. It was shown in our previous research that introduction of additional hydroxyl groups into the stilbene structure increases the biological activity of resveratrol. In this study, the activity of 3,3?,4,4?,5,5?-hexahydroxystilbene (M8) was investigated in ZR-75-1, MDA-MB-231 and T47D human

Marek Murias; Michal W. Luczak; Anna Niepsuj; Violetta Krajka-Kuzniak; Malgorzata Zielinska-Przyjemska; Pawel P. Jagodzinski; Walter Jäger; Thomas Szekeres; Jadwiga Jodynis-Liebert

2008-01-01

265

Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes  

Microsoft Academic Search

Molecular subtypes of breast cancer with relevant bio- logical and clinical features have been defined recently, notably ERBB2-overexpressing, basal-like, and luminal- like subtypes. To investigate the ability of mass spec- trometry-based proteomics technologies to analyze the molecular complexity of human breast cancer, we per- formed a SELDI-TOF MS-based protein profiling of hu- man breast cell lines (BCLs). Triton-soluble proteins from

Anthony Goncalves; Emmanuelle Charafe-Jauffret; Francois Bertucci; Stephane Audebert; Yves Toiron; Benjamin Esterni; Florence Monville; Carole Tarpin; Jocelyne Jacquemier; Gilles Houvenaeghel; Christian Chabannon; Jean-Marc Extra; Patrice Viens; Jean-Paul Borg; D. Birnbaum

2008-01-01

266

Loss of heterozygosity of the L-myc oncogene in human breast tumors  

Microsoft Academic Search

Recent studies suggest that loss of heterozygosity may play an important role in various human neoplasia. Cytogenetic abnormalities detected in primary breast tumors led us to examine breast tumor DNAs for deletions. In the present study, we demonstrate, using restriction fragment length polymorphism (RFLP) analysis at the L-myc proto-oncogene (chromosome 1p32), a frequent loss of heterozygosity in primary breast tumor

Ivan Bieche; Marie-Helene Champeme; Giorgio Merlo; Christian-Jacques Larsen; Robert Callahan; Rosette Lidereau

1990-01-01

267

Altered promoter usage characterizes monoallelic transcription arising withERBB2 amplification in human breast cancers  

Microsoft Academic Search

Analysis of a collection of human breast cancers (n = 150), enriched in ERBB2-positive cases (n = 57) and involving tumor gen- otyping relative to population-matched blood genotyping (n = 749) for a common ERBB2 single nucleotide polymorphism Ala(G)1170Pro(C), revealed that ERBB2 amplification in breast cancer is invariably monoallelic. Analysis of paired breast cancer and blood samples from informative (G1170C

Christopher C. Benz; Vita Fedele; Fan Xu; Bauke Ylstra; David Ginzinger; Mamie Yu; Dan Moore; Rayna Kneuper Hall; Daynna J. Wolff; Mary L. Disis; Serenella Eppenberger-Castori; Urs Eppenberger; Francesco Schittulli; Stefania Tommasi; Angelo Paradiso; Gary K. Scott; Donna G. Albertson

2006-01-01

268

Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival  

PubMed Central

Introduction The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Methods Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. Results In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Conclusions Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs through uncoupling of serotonin from the homeostatic regulatory mechanisms of the normal mammary epithelium. The findings open a new avenue for identification of diagnostic and prognostic markers, and valuable new therapeutic targets for managing breast cancer.

2009-01-01

269

Prolactin-Stimulated Activation of ERK1/2 Mitogen-Activated Protein Kinases is Controlled by PI3-Kinase/Rac/PAK Signaling Pathway in Breast Cancer Cells  

PubMed Central

There is strong evidence that deregulation of prolactin (PRL) signaling contributes to pathogenesis and chemoresistance of breast cancer. Therefore, understanding cross-talk between distinct signal transduction pathways triggered by activation of the prolactin receptor (PRL-R), is essential for elucidating the pathogenesis of metastatic breast cancer. In this study, we applied a sequential inhibitory analysis of various signaling intermediates to examine the hierarchy of protein interactions within the PRL signaling network and to evaluate the relative contributions of multiple signaling branches downstream of PRL-R to the activation of the extracellular signal-regulated kinases ERK1 and ERK2 in T47D and MCF-7 human breast cancer cells. Quantitative measurements of the phosphorylation/activation patterns of proteins showed that PRL simultaneously activated Src family kinases (SFKs) and the JAK/STAT, phosphoinositide-3 (PI3)-kinase/Akt and MAPK signaling pathways. The specific blockade or siRNA-mediated suppression of SFK/FAK, JAK2/STAT5, PI3-kinase/PDK1/Akt, Rac/PAK or Ras regulatory circuits revealed that (1) the PI3-kinase/Akt pathway is required for activation of the MAPK/ERK signaling cascade upon PRL stimulation; (2) PI3-kinase-mediated activation of the c-Raf-MEK1/2-ERK1/2 cascade occurs independent of signaling dowstream of STATs, Akt and PKC, but requires JAK2, SFKs and FAK activities; (3) activated PRL-R mainly utilizes the PI3-kinase-dependent Rac/PAK pathway rather than the canonical Shc/Grb2/SOS/Ras route to initiate and sustain ERK1/2 signaling. By interconnecting diverse signaling pathways PLR may enhance proliferation, survival, migration and invasiveness of breast cancer cells.

Aksamitiene, Edita; Achanta, Sirisha; Kolch, Walter; Kholodenko, Boris N.; Hoek, Jan B.; Kiyatkin, Anatoly

2011-01-01

270

Estradiol stimulates c- myc proto-oncogene expression in normal human breast epithelial cells in culture  

Microsoft Academic Search

The proto-oncogene c-myc is involved in the stimulation of cell proliferation, and its expression is known to be stimulated by estradiol (E2) in human breast cancer cell lines and various non-cancerous E2-dependent tissues. However, little information is currently available concerning its expression and regulation in normal human breast tissue. We therefore studied c-myc expression and hormone modulation in normal human

Etienne Leygue; Rosita Gol-Winkler; Anne Gompel; Christine Louis-Sylvestre; Laurence Soquet; Sylvain Staub; Frederique Kuttenn; Pierre Mauvais-Jarvis

1995-01-01

271

The emerging importance of ?-L-fucose in human breast cancer: a review  

PubMed Central

Breast cancer cells incorporate the simple sugar alpha-L-fucose (fucose) into glycoproteins and glycolipids which, in turn, are expressed as part of the malignant phenotype. We have noted that fucose is not simply a bystander molecule, but, in fact, contributes to many of the fundamental oncologic properties of breast cancer cells. Here, we summarize the evidence from us and others that fucose is necessary for key functions of neoplastic progression including hematogenous metastasis, tumor invasion through extracellular matrices including basement membranes and up-regulation of the Notch signaling system, with implications for epithelial-to-mesenchymal transition and activation of breast cancer stem cells. Additionally, certain breast cancer biomarkers are fucose-rich while a well-known marker of breast cancer progression, soluble E-selectin, is a known counter-receptor of fucosylated selectin ligands. We provide illustrative examples and supportive evidence drawn from work with human breast cancer cell lines in vitro as well as clinical studies with human pathologic material. And finally, we discuss evidence that fucose (or its absence) is central to the mechanisms of action of several experimental targeted therapies which may prove useful in breast cancer treatment. We propose that alpha-L-fucose is essential in order to construct first, the malignant and then the metastatic phenotype of many human breast cancers. This knowledge may inform the search for novel treatment approaches in breast cancer.

Listinsky, Jay J; Siegal, Gene P; Listinsky, Catherine M

2011-01-01

272

Cloning and expression of full-length cDNA encoding human vitamin D receptor  

Microsoft Academic Search

Complementary DNA clones encoding the human vitamin D receptor have been isolated from human intestine and T47D cell cDNA libraries. The nucleotide sequence of the 4605-base pair (bp) cDNA includes a noncoding leader sequence of 115 bp, a 1281-bp open reading frame, and 3209 bp of 3â² noncoding sequence. Two polyadenylylation signals, AATAAA, are present 25 and 70 bp upstream

A. R. Baker; D. P. McDonnell; M. Hughes; T. M. Crisp; D. J. Mangelsdorf; M. R. Haussler; J. W. Pike; J. Shine; B. W. OMalley

1988-01-01

273

Recombinant GnRH-p53 protein sensitizes breast cancer cells to 5-fluorouracil-induced apoptosis in vitro and in vivo.  

PubMed

An ideal approach to treat cancers with dysfunctional p53 tumor suppressor gene is to reinstate p53 functionality by directly using p53 protein as a therapeutic agent. However, this has not been possible because the cells cannot readily internalize the protein. We constructed a fusion protein consisting of gonadotropin-releasing hormone (GnRH-p53) and p53 moieties. The recombinant protein was directly used to treat human breast cancer cells and athymic nude mice bearing breast cancer xenografts, with or without DNA synthesis-arresting agent 5-fluorouracil (5-FU). Treatments of cells from breast cancer cell-lines MDA-MB-231, T47D, or SKBR-3 with GnRH-p53 in combination with 5-FU significantly enhanced p53-activated apoptosis signals, including PUMA expression, BAX translocation to mitochondria, and activated caspase-3. Intratumoral injection of the GnRH-p53 protein inhibited MDA-MB-231 xenograft growth and induced p53-mediated apoptosis in the tumors. Systemic treatment of the tumor-bearing mice via tail vein injection of GnRH-p53 markedly augmented the anticancer efficacy of 5-FU. Substitution of GnRH-p53 with wild type p53 protein had no effect. Recombinant GnRH-p53 is able to function as a surrogate of p53 with regard to its apoptosis-inducing activity. Combination of GnRH-p53 with DNA-damaging drugs may be of important therapeutic value for cancer treatment. PMID:23801079

Lu, Yi; Zhang, Zhisong; Yan, Zhenwen; Chen, Li; Deng, Weimin; Lotze, Michael; Wang, Zhou; Lin, Xinli; Li, Lu-Yuan

2013-10-01

274

Mechanism of Retinoid Response in Human Breast Cancer.  

National Technical Information Service (NTIS)

Retinoids, the natural and synthetic vitamin A derivatives, are well known for their inhibitory effect on the proliferation of breast cancer cells. However, the growth inhibitory effect of retinoids appears to diminish during progression of breast tumor a...

X. K. Zhang

1995-01-01

275

Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth.  

PubMed Central

Breast cancers often progress from a hormone-dependent, nonmetastatic, antiestrogen-sensitive phenotype to a hormone-independent, antiestrogen- and chemotherapy-resistant phenotype with highly invasive and metastatic growth properties. This progression is usually accompanied by altered function of the estrogen receptor (ER) or outgrowth of ER-negative cancer cells. To understand the molecular mechanisms responsible for metastatic growth of ER-negative breast cancers, the activities of the transcription factor NF-kappaB (which modulates the expression of genes involved in cell proliferation, differentiation, apoptosis, and metastasis) were compared in ER-positive (MCF-7 and T47-D) and ER-negative (MDA-MB-231 and MDA-MB-435) human breast cancer cell lines. NF-kappaB, which is usually maintained in an inactive state by protein-protein interaction with inhibitor IkappaBs, was found to be constitutively active in ER-negative breast cancer cell lines. Constitutive DNA binding of NF-kappaB was also observed with extracts from ER-negative, poorly differentiated primary breast tumors. Progression of the rat mammary carcinoma cell line RM22-F5 from an ER-positive, nonmalignant phenotype (E phenotype) to an ER-negative, malignant phenotype (F phenotype) was also accompanied by constitutive activation of NF-kappaB. Analysis of individual subunits of NF-kappaB revealed that all ER-negative cell lines, including RM22-F5 cells of F phenotype, contain a unique 37-kDa protein which is antigenically related to the RelA subunit. Cell-type-specific differences in IkappaB alpha, -beta, and -gamma were also observed. In transient-transfection experiments, constitutive activity of an NF-kappaB-dependent promoter was observed in MDA-MB-231 and RM22-F5 cells of F phenotype, and this activity was efficiently repressed by cotransfected ER. Since ER inhibits the constitutive as well as inducible activation function of NF-kappaB in a dose-dependent manner, we propose that breast cancers that lack functional ER overexpress NF-kappaB-regulated genes. Furthermore, since recent data indicate that NF-kappaB protects cells from tumor necrosis factor alpha-, ionizing radiation-, and chemotherapeutic agent daunorubicin-mediated apoptosis, our results provide an explanation for chemotherapeutic resistance in ER-negative breast cancers.

Nakshatri, H; Bhat-Nakshatri, P; Martin, D A; Goulet, R J; Sledge, G W

1997-01-01

276

The nude mouse as an in vivo model for human breast cancer invasion and metastasis  

Microsoft Academic Search

Summary Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains of immune-deficient mice in terms of providing a model for studies of the invasive

Nils Briinner; Birgitte Boysen; John Rømer; Mogens Spang-Thomsen

1993-01-01

277

HET is a Novel Tumor Suppressor Gene in Human Breast Cancer.  

National Technical Information Service (NTIS)

We have evidence that the nuclear matrix protein RET might represent an important tumor suppressor gene in human breast cancer: (1) Overexpression of HET inhibited growth. (2) it was negatively associated with S-phase fraction in breast tumors, and 16% of...

S. Oesterreich

2000-01-01

278

Induction of Transforming Growth Factor 0, in Human Breast Cancer in Vivo following Tamoxifen Treatment  

Microsoft Academic Search

We have investigated the ability of tamoxifen to regulate members of the transforming growth factor ß (TGF-\\/Ï) family in human breast can cers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extra cellular TGF-01 in breast cancer biopsies, compared with matched pre treatment samples from the same patient. The induced

Anju Butta; Kenneth MacLennan; Kathleen C. Flanders; Nigel P. M. Sacks; Ian Smith; Alan McKinna; Mitchell Dowsett; Lalage M. Wakefield; Michael B. Sporn; Michael Baum; Anthony A. Colletta

279

Copper, lead and zinc concentrations of human breast milk as affected by maternal dietary practices  

Microsoft Academic Search

Maternal dietary practices have been found to affect the concentrations of some nutrients in human breast milk. Lead toxicity is a concern in young children. Lead, copper and zinc are thought to compete for intestinal absorption sites. The objective of the current project was to compare copper, lead and zinc contents of breast milk from practicing lacto-vegetarian and omnivore, lactating

J. Umoren; C. Kies

1986-01-01

280

Examination of a Newly Discovered Human Retrovirus, XMRV, in Breast Cancer.  

National Technical Information Service (NTIS)

The main objective of this research project is to test the hypothesis that a newly discovered retrovirus, XMRV, is involved development of human breast cancer. To accomplish this, XMRV protein and nucleic acid will be detected in breast cancer specimens t...

F. K. Yoshimura

2011-01-01

281

Development of a new human breast cancer cell line Ia270  

Microsoft Academic Search

Summary A new human breast cancer cell line (Ia-270) has been isolated from a malignant pleural effusion from a woman with metastatic infiltrating ductal carcinoma of the breast. This cell line contains cytoplasmic estrogen (ER) and progesterone (PR) receptors. Following estradiol (E2) administration, PR synthesis is augmented and a higher level of saturation density is reached. In an athymic mouse,

Pao-Min Loh; Gerald Clamon; John MacIndoe; Mark White; Luis Urdaneta; Bharati Hukku; Ward D. Peterson

1985-01-01

282

Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome  

Microsoft Academic Search

INTRODUCTION: To investigate the expression of EPLIN-?, epithelial protein lost in neoplasm, in human breast cancer tissues\\/cells and investigate the cellular impact of EPLIN-? on breast cancer cells. EXPERIMENTAL DESIGN: EPLIN-? was determined in tumour (n = 120) and normal mammary tissues (n = 32), and cancer cell lines (n = 16). Cell invasion, in vitro and in vivo growth

Wen G Jiang; Tracey A Martin; Jonathan M Lewis-Russell; Anthony Douglas-Jones; Lin Ye; Robert E Mansel

2008-01-01

283

Identification of Cellular Binding Sites for a Novel Human Anti-Breast Cancer Peptide.  

National Technical Information Service (NTIS)

We have synthesized a nine amino acid peptide (COP) that inhibits the growth of ER+ human breast. COP does not act like Tam or any other known agent currently used to treat ER+ breast cancer. Understanding the process by which COP mediates its inhibitory ...

L. A. DeFreest J. A. Bennett

2003-01-01

284

Detection of an Antigen Related to Mason-Pfizer Virus in Malignant Human Breast Tumors  

Microsoft Academic Search

An antigen related to the major structural protein (p27) of Mason-Pfizer monkey virus has been found in malignant human breast tumors by radioimmunoassays. This antigen was not detected in normal placental tissues or in tumors that were not of breast origin.

J. Yeh; M. Ahmed; S. A. Mayyasi; A. Alessi

1975-01-01

285

Examination of a Newly Discovered human Retrovirus, XMRV, in Breast Cancer.  

National Technical Information Service (NTIS)

The main objective of this research project is to test the hypothesis that a newly discovered retrovirus, XMRV, is involved in the development of human breast cancer. To accomplish this, we have examined XMRV infection in breast cancer tissue in compariso...

F. K. Yoshimura

2012-01-01

286

Growth Inhibitory Activity of Extracts and Purified Components of Black Cohosh on Human Breast Cancer Cells  

Microsoft Academic Search

The purpose of this study was to determine whether black cohosh contains constituents that inhibit the growth of human breast cancer cells, and therefore might eventually be useful in the prevention or treatment of breast cancer. Black cohosh rhizomes were extracted with methanol\\/water and fractionated by solvent–solvent partitioning to yield three fractions: hexane, ethyl acetate and water. The ethyl acetate

Linda Saxe Einbond; Masahito Shimizu; Danhua Xiao; Paiboon Nuntanakorn; Jin T. E. Lim; Masumi Suzui; Colette Seter; Thomas Pertel; Edward J. Kennelly; Fredi Kronenberg; I. Bernard Weinstein

2004-01-01

287

Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer  

SciTech Connect

Pleiotrophin (PTN, Ptn) is an 18 kDa cytokine expressed in human breast cancers. Since inappropriate expression of Ptn stimulates progression of breast cancer in transgenic mice and a dominant negative PTN reverses the transformed phenotype of human breast cancer cells that inappropriately express Ptn, it is suggested that constitutive PTN signaling in breast cancer cells that inappropriately express Ptn activates pathways that promote a more aggressive breast cancer phenotype. Pleiotrophin signals by inactivating its receptor, the receptor protein tyrosine phosphatase (RPTP){beta}/{zeta}, and, recently, PTN was found to activate anaplastic lymphoma kinase (ALK) through the PTN/RPTP{beta}/{zeta} signaling pathway in PTN-stimulated cells, not through a direct interaction of PTN with ALK and thus not through the PTN-enforced dimerization of ALK. Since full-length ALK is activated in different malignant cancers and activated ALK is a potent oncogenic protein, we examined human breast cancers to test the possibility that ALK may be expressed in breast cancers and potentially activated through the PTN/RPTP{beta}/{zeta} signaling pathway; we now demonstrate that ALK is strongly expressed in different histological subtypes of human breast cancer; furthermore, ALK is expressed in both nuclei and cytoplasm and, in the 'dotted' pattern characteristic of ALK fusion proteins in anaplastic large cell lymphoma. This study thus supports the possibility that activated ALK may be important in human breast cancers and potentially activated either through the PTN/RPTP{beta}/{zeta} signaling pathway, or, alternatively, as an activated fusion protein to stimulate progression of breast cancer in humans.

Perez-Pinera, Pablo [The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (United States); Chang, Y. [The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (United States); Astudillo, A. [Hospital Universitario Central de Asturias, Oviedo (Spain); Mortimer, J. [Moore's Cancer Center, University of California San Diego, San Diego, CA (United States); Deuel, T.F. [The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (United States)]. E-mail: tfdeuel@scripps.edu

2007-06-29

288

Boron-Based 4-Hydroxytamoxifen Bioisosteres for Treatment of de Novo Tamoxifen Resistant Breast Cancer  

PubMed Central

Tamoxifen remains the first line therapy for estrogen receptor positive (ER+) breast cancer. However, polymorphisms of the gene encoding P450 2D6 could result in no protein expression or no CYP2D6 enzymatic activity and may significantly reduce the benefit of the hormone therapy. To address this issue, we designed and synthesized three 4-hydroxytamoxifen bioisosteres utilizing a boron-aryl carbon bond that can be oxidized under physiological conditions to yield 4-hydroxytamoxifen. We show that the bioisosteres inhibit the growth of two ER+ breast cancer cell lines, MCF-7 and T47D, with potencies comparable to or greater than that of 4-hydroxytamoxifen. We further demonstrate that after incubation with breast cancer cells, the majority of the bioisosteres has been converted to 4-hydroxytamoxifen. Our study suggests that boron-based 4-hydroxytamoxifen bioisosteres may be an effective therapeutic remedy for intrinsic tamoxifen resistance in breast cancer patients deficient in CYP2D6 metabolism.

Jiang, Quan; Zhong, Qiu; Zhang, Qiang; Zheng, Shilong; Wang, Guangdi

2012-01-01

289

Ocular Input for Human Melatonin Regulation: Relevance to Breast Cancer  

Microsoft Academic Search

light; melatonin; cancer; photoreceptor; circadian; action spectrum Abstract The impact of breast cancer on women across the world has been extensive and severe. As prevalence of breast cancer is greatest in industrialized regions, exposure to light at night has been proposed as a potential risk factor. This theory is supported by the epidemiological observations of decreased breast cancer in blind

Gena Glickman; Robert Levin; George C. Brainard

2002-01-01

290

The breast\\/nipple\\/areola complex and human sexuality  

Microsoft Academic Search

The male or female breast\\/nipple\\/areola complex arises from a common mammary stem cell and develops similarly in the foetus and during infancy. At puberty the male's breasts remain rudimentary but the female's develop further, mainly through oestrogen and progesterone stimulation, and become more sensitive. Female breasts serve both nutritive and sexual functions, unlike other primates they develop at puberty before

Roy J. Levin

2006-01-01

291

A high-content assay to identify small-molecule modulators of a cancer stem cell population in luminal breast cancer.  

PubMed

Breast cancers expressing hormone receptors for estrogen (ER) and progesterone (PR) represent ~70% of all cases and are treated with both ER-targeted and chemotherapies, with near 40% becoming resistant. We have previously described that in some ER(+) tumors, the resistant cells express cytokeratin 5 (CK5), a putative marker of breast stem and progenitor cells. CK5(+) cells have lost expression of ER and PR, express the tumor-initiating cell surface marker CD44, and are relatively quiescent. In addition, progestins, which increase breast cancer incidence, expand the CK5(+) subpopulation in ER(+)PR(+) breast cancer cell lines. We have developed models to induce and quantitate CK5(+)ER(-)PR(-) cells, using CK5 promoter-driven luciferase (Fluc) or green fluorescent protein (GFP) reporters stably transduced into T47D breast cancer cells (CK5Pro-GFP or CK5Pro-Luc). We validated the CK5Pro-GFP-T47D model for high-content screening in 96-well microplates and performed a pilot screen using a focused library of 280 compounds from the National Institutes of Health clinical collection. Four hits were obtained that significantly abrogated the progestin-induced CK5(+) cell population, three of which were members of the retinoid family. Hence, this approach will be useful in discovering small molecules that could potentially be developed as combination therapies, preventing the acquisition of a drug-resistant subpopulation. PMID:22751729

Yoo, Byong Hoon; Axlund, Sunshine Daddario; Kabos, Peter; Reid, Brian G; Schaack, Jerome; Sartorius, Carol A; LaBarbera, Daniel V

2012-06-29

292

Quality assurance/quality control procedures for chlorinated hydrocarbons in human breast adipose tissue  

SciTech Connect

Extensive literature exists supporting the accumulation of organochlorine pesticides such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane], and polychlorinated biphenyls (PCBs) in human adipose tissue. Debate has surfaced concerning the link between these environmental contaminants and human breast cancer. Accurate residue analysis and proper analytical procedures are critical in determining the extent to which these compounds play a role in human breast cancer. Further, adequate quality assessment/quality control (QA/QC) is critical for reliable residue analysis. The purpose of this research was twofold: (1) to find an appropriate surrogate for human breast adipose tissue for spiking purposes, as human samples are difficult to obtain, and (2) to develop a human breast adipose tissue pool that yields adequate reproducibility with low coefficients of variation (CVs) for each compound of interest. Using a previously validated method developed in the Analytical Laboratory at Colorado State University, rendered ovine adipose tissue was found to be a suitable spiking material, as it was free of interfering compounds and behaved in a manner similar to human breast adipose tissue throughout the analytical method. Further, this analytical method was used to produce data on three control pool preparations: (A) blended human breast adipose tissue (n = 26), (B) blended and partially rendered human breast adipose tissue (n = 12), and (C) fully blended and rendered human breast adipose tissue (n = 15). The CVs between control pools vary up to 20% for a single compound. The most reproducible preparation procedure requires full blending and rendering. 26 refs., 1 fig., 5 tabs.

Archibeque-Engle, S.; Tessari, J.D.; Winn, D.T. [Colorado State Univ., Fort Collins, CO (United States)

1996-12-27

293

Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer  

Microsoft Academic Search

Monoclonal antibodies against two epitopes of FGFR-1 have been used to investigate FGFR-1 expression in the normal and neoplastic human breast. Different forms are detected in the different cell types constituting the normal breast. Moreover, breast cancer cells lack one form of FGFR-1. Western blot analysis showed 115-kDa and 106-kDa forms of FGFR-1 within the human breast. The 115-kDa band

C Yiangou; H Cox; GS Bansal; R Coope; JJ Gomm; R Barnard; J Walters; N Groome; S Shousha; RC Coombes; CL Johnston

1997-01-01

294

Characterization of viral particles isolated from primary cultures of human breast cancer cells.  

PubMed

The association of human breast cancer with sequences similar to the mouse mammary tumor virus (MMTV) has been shown, but convincing evidence for the presence of viral particles in breast tumors has been lacking. We have described the complete proviral structure of a retrovirus in human breast cancer. This provirus, designated as human mammary tumor virus (HMTV), was 95% homologous to MMTV and revealed features of a replication-competent virus. We have therefore investigated the production of viral particles in primary cultures of human breast cancer (MSSM). Cells isolated from ascites or pleural effusions of patients with metastatic breast cancer contained viral sequences in their DNA, expressed Env protein, and showed retroviral particles by electron microscopy. Viral particles from culture media exhibited morphologic features of beta-retroviruses sedimenting at buoyant densities of 1.12 to 1.18 g/mL in sucrose gradients and showed reverse transcriptase activity. cDNA sequences from virion RNA were synthesized, amplified, and sequenced and all the virion genes were detected and 70% of the virion RNA was sequenced. The sequence homologies were, respectively, 85% to 95% compared with the MMTV and HMTV proviruses we have previously described. These results clearly show that breast cancer cells in primary cultures produced HMTV viral particles that are similar to the mouse virus and which may play a role in human breast cancer pathogenesis. PMID:17875739

Melana, Stella M; Nepomnaschy, Irene; Sakalian, Michael; Abbott, Andrea; Hasa, Jennifer; Holland, James F; Pogo, Beatriz G T

2007-09-15

295

Leukemia inhibitory factor binds to human breast cancer cells and stimulates their proliferation.  

PubMed

Leukemia inhibitory factor (LIF) is a cytokine that was originally described as a differentiation factor of a murine myeloid leukemia cell line and subsequently found to be an important mediator of embryonic development. Although extensively studied in the hematopoietic system, its effects on solid tumors are generally unknown. In the present study we investigated the role of LIF in human breast cancer cells. Using the reverse transcriptase-polymerase chain reaction, we found that the human breast carcinoma MCF-7 cell line expressed the message for both LIF receptor and its signal-transducing protein gp130, suggesting that these receptors might be biologically active. Binding studies with radiolabeled LIF demonstrated that MCF-7 cells interacted with this cytokine, and the ligand binding was specific and time, dose, and temperature dependent. In addition, a Scatchard analysis of the data revealed a single class of high-affinity (Kd 0.27 nM) receptors with a density of approximately 430 sites per cell. MCF-7 cells exposed to LIF internalized and degraded the ligand. LIF stimulated the growth of MCF-7 as well as other estrogen-dependent and independent breast cancer cell lines, but the effect on normal breast epithelial lines was less significant. Likewise, it stimulated colony formation by breast cancer cells obtained from five different breast cancer patients in a dose-dependent fashion. These results overall suggest that human breast tumor cells express functional LIF receptors that play a role in breast cancer cell proliferation. PMID:8564713

Estrov, Z; Samal, B; Lapushin, R; Kellokumpu-Lehtinen, P; Sahin, A A; Kurzrock, R; Talpaz, M; Aggarwal, B B

1995-10-01

296

Repression of RTK Recycling Pathway By SLUG in Human Breast Tumor Cells.  

National Technical Information Service (NTIS)

We hypothesize that the transcriptional repressor protein SLUG down regulates some key components of the dynein/dynactin pathway of RTK internalization in human breast tumor cells resulting in increase in the surface levels of these receptors, thus adding...

G. Chaudhuri

2010-01-01

297

Laser capture microdissection and advanced molecular analysis of human breast cancer.  

PubMed

Advances in comprehensive genomic and proteomic technologies are providing researchers with an unprecedented opportunity for high-throughput molecular analysis of human breast cancer. Adaptation of these technologies to laser capture microdissection (LCM) is poised to exert dramatic change on the pace of breast cancer research. Although technical limitations have impeded the coupling of these high-throughput technologies to LCM, recent advances have allowed for the successful application of this cellular-based approach to breast cancer, and the results of such studies have provided researchers with unique insight into the disease. This approach holds great potential for rapid advancement in our understanding of breast cancer, and it is hoped that such advancements will lead to novel predictive and therapeutic strategies for women with the disease. This review outlines the current status of the adaptation of advanced molecular technologies to LCM and highlights recent studies in which this approach has been applied to human breast cancer. PMID:14973377

Fuller, Andrew P; Palmer-Toy, Darryl; Erlander, Mark G; Sgroi, Dennis C

2003-07-01

298

From The Cover: Reconstruction of functionally normal and malignant human breast tissues in mice  

NASA Astrophysics Data System (ADS)

The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

Kuperwasser, Charlotte; Chavarria, Tony; Wu, Min; Magrane, Greg; Gray, Joe W.; Carey, Loucinda; Richardson, Andrea; Weinberg, Robert A.

2004-04-01

299

Human breast milk is a rich source of multipotent mesenchymal stem cells  

Microsoft Academic Search

Putative stem cells have been isolated from various tissue fluids such as synovial fluid, amniotic fluid, menstrual blood,\\u000a etc. Recently the presence of nestin positive putative mammary stem cells has been reported in human breast milk. However,\\u000a it is not clear whether they demonstrate multipotent nature. Since human breast milk is a non-invasive source of mammary stem\\u000a cells, we were

Satish Patki; Sachin Kadam; Vikash Chandra; Ramesh Bhonde

2010-01-01

300

Growth inhibition and apoptotic effect of alpha-eleostearic acid on human breast cancer cells  

Microsoft Academic Search

Alpha-eleostearic acid (?-ESA) is a natural and biologically active compound which possesses potent antioxidant and anti-tumor\\u000a activity. The purpose of this study was to confirm the anticancer activity of ?-ESA against human breast cancer cells and\\u000a to further elucidate its mechanism of activity. Human breast cancer cells and normal liver cells were used for in-vitro tests\\u000a of the anticancer activity

Tingting ZhangYanping; Yanping Gao; Yu Mao; Quanbo Zhang; Caiyu Lin; Ping Lin; Jie Zhang; Xiujie Wang

301

Relation of cell proliferation to expression of peripheral benzodiazepine receptors in human breast cancer cell lines  

Microsoft Academic Search

Peripheral benzodiazepine receptor (PBR) agonist [3H]Ro5-4864 has been shown to bind with high affinity to the human breast cancer cell line BT-20. Therefore, we investigated different human breast cancer cell lines with regard to binding to [3H]Ro5-4864 and staining with the PBR-specific monoclonal antibody 8D7. Results were correlated with cell proliferation characteristics. In flow cytometric analysis, the estrogen receptor (ER)-negative

Anne Beinlich; Renate Strohmeier; Manfred Kaufmann; Herbert Kuhl

2000-01-01

302

Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status  

Microsoft Academic Search

Potential antiproliferative effects of tocotrienols, the major vitamin E component in palm oil, were investigated on the growth\\u000a of both estrogen-responsive (ER+) MCF7 human breast cancer cells and estrogen-unresponsive (ER-) MDA-MD-231 human breast cancer\\u000a cells, and effects were compared with those of ?-tocopherol (?T). The tocotrienol-rich fraction (TRF) of palm oil inhibited\\u000a growth of MCF7 cells in both the presence

Kalanithi Nesaretnam; Ruth Stephen; Ray Dils; Philippa Darbre

1998-01-01

303

Near-infrared laser speckle imaging of human breast tissue  

NASA Astrophysics Data System (ADS)

Current methods of breast cancer diagnostics (self-exam, clinical exam, x-ray mammography) fail to diagnose a significant number of cases while still in readily operable stages. This is especially true in younger women, where fibrotic tissue reduces the efficacy of x-ray mammography. Near infrared (NIR) laser photons pass diffusively through human tissue, creating a speckle pattern in a detector after transmission. The high and low intensity variations of the speckle have the appearance of random noise, but are not. The speckle pattern will have an intensity distribution that is informative about the scattering and absorption properties of the tissue that is imaged. Adaptations to the Los Alamos National Laboratory MCNP code are described that allow simulation of NIR laser transport through human tissue. A HeNe laser was used to create laser intensity patterns via transmission through homogeneous and non-homogeneous tissue phantoms. The Kolmogorov-Smirnov test was used to compare the cumulative distribution functions of the laser intensity patterns, and identify the presence of a non-homogeneity. Laser speckle techniques offer the ability to image tumors with few (<3) millimeter resolution without ionizing radiation dose.

Bean, Robert Speer

304

Comparative Studies of Manganese Binding in Human Breast Milk, Bovine Milk and Infant Formula1  

Microsoft Academic Search

The difference in ligand localization of manganese in human breast milk, cow's milk and infant formula was investigated. Extrinsic labeling technique was used and the different manganese-binding ligands were separated by gel permeation column chromatography. Manganese was found to bind to different ligands in human milk, cow's milk and infant formula. In human milk, manganese was bound by two high

WAI-YEE CHAN; JAMES M. BATES; J. R. ANDOWEN; M. RENNERT

305

Human-Compatible Animal Models for Preclinical Research on Hormones in Breast Cancer.  

National Technical Information Service (NTIS)

Our most significant findings during the second year of work included the following: (1) The PRL-humanized mice synthesize and secrete hPRL that is fully biologically active at the human PRL receptor as evidenced by activation of STAT5 in human breast can...

K. A. Gregerson

2012-01-01

306

Combined photoacoustic and ultrasound imaging of human breast in vivo in the mammographic geometry  

NASA Astrophysics Data System (ADS)

This photoacoustic volume imaging (PAVI) system is designed to study breast cancer detection and diagnosis in the mammographic geometry in combination with automated 3D ultrasound (AUS). The good penetration of near-infrared (NIR) light and high receiving sensitivity of a broad bandwidth, 572 element, 2D PVDF array at a low center-frequency of 1MHz were utilized with 20 channel simultaneous acquisition. The feasibility of this system in imaging optically absorbing objects in deep breast tissues was assessed first through experiments on ex vivo whole breasts. The blood filled pseudo lesions were imaged at depths up to 49 mm in the specimens. In vivo imaging of human breasts has been conducted. 3D PAVI image stacks of human breasts were coregistered and compared with 3D ultrasound image stacks of the same breasts. Using the designed system, PAVI shows satisfactory imaging depth and sensitivity for coverage of the entire breast when imaged from both sides with mild compression in the mammographic geometry. With its unique soft tissue contrast and excellent sensitivity to the tissue hemodynamic properties of fractional blood volume and blood oxygenation, PAVI, as a complement to 3D ultrasound and digital tomosynthesis mammography, might well contribute to detection, diagnosis and prognosis for breast cancer.

Xie, Zhixing; Lee, Won-Mean; Hooi, Fong Ming; Fowlkes, J. Brian; Pinsky, Renee W.; Mueller, Dean; Wang, Xueding; Carson, Paul L.

2013-03-01

307

MicroRNA-221/222 Negatively Regulates Estrogen Receptor? and Is Associated with Tamoxifen Resistance in Breast Cancer*  

PubMed Central

A search for regulators of estrogen receptor ? (ER?) expression has yielded a set of microRNAs (miRNAs) for which expression is specifically elevated in ER?-negative breast cancer. Here we show distinct expression of a panel of miRNAs between ER?-positive and ER?-negative breast cancer cell lines and primary tumors. Of the elevated miRNAs in ER?-negative cells, miR-221 and miR-222 directly interact with the 3?-untranslated region of ER?. Ectopic expression of miR-221 and miR-222 in MCF-7 and T47D cells resulted in a decrease in expression of ER? protein but not mRNA, whereas knockdown of miR-221 and miR-222 partially restored ER? in ER? protein-negative/mRNA-positive cells. Notably, miR-221- and/or miR-222-transfected MCF-7 and T47D cells became resistant to tamoxifen compared with vector-treated cells. Furthermore, knockdown of miR-221 and/or miR-222 sensitized MDA-MB-468 cells to tamoxifen-induced cell growth arrest and apoptosis. These findings indicate that miR-221 and miR-222 play a significant role in the regulation of ER? expression at the protein level and could be potential targets for restoring ER? expression and responding to antiestrogen therapy in a subset of breast cancers.

Zhao, Jian-Jun; Lin, Jianhong; Yang, Hua; Kong, William; He, Lili; Ma, Xu; Coppola, Domenico; Cheng, Jin Q.

2008-01-01

308

Microarray determination of Bcl-2 family protein inhibition sensitivity in breast cancer cells.  

PubMed

This study tests the hypothesis that reverse transcription polymerase chain reaction (RT-PCR) microarrays can be used to predict the relative sensitivity to induction of apoptosis in breast cancer cells exposed to inhibitors of antiapoptotic Bcl-2 family proteins. Four cell lines, MDA-MB-231 (MDA-231) and MDA-MB-468 (MDA-468), BT-20 and T47-D were screened for relative expression of Bcl-2 family members A1, Mcl-1, Bcl-2, Bcl-xL and Bcl-w mRNA by RT-PCR microarrays and Western analysis. The four cell lines were treated with 1 ?mol/L obatoclax (GX15-070) and/or 2 Gy radiation (RT) and monitored for apoptosis after 48 h. Cell lines showing the highest total fold-increase of Bcl-2 family member mRNA, MDA-231 and MDA-468, also showed the highest levels of apoptosis induction (approximately 70% with obatoclax alone and 82% with obatoclax plus RT). Cell lines with little or no increase in Bcl-2 family mRNA (BT-20 and T47-D) showed less apoptosis (30% following treatment with obatoclax and 42% with obatoclax plus RT). RT-PCR arrays can predict the relative apoptosis response of breast cancer cells to the pan Bcl-2 inhibitor obatoclax alone or when combined with radiation. PMID:23576806

Hudson, Sandra G; Halleran, Devin R; Nevaldine, Barbara; Shapiro, Anna; Hutchison, Robert E; Hahn, Peter J

2013-02-01

309

Decreased expression of human D-glucuronyl C5-epimerase in breast cancer.  

PubMed

D-glucuronyl C5-epimerase (GLCE) is one of the key enzymes in proteoglycan biosynthesis. However, nothing is known about expression and activity of the protein in cancer. In this study, we investigated GLCE expression in human breast cancer using multipex RT-PCR, QRT-PCR and Western-blot assays. In total, 21 patients without malignancy and 74 patients with breast tumor were investigated. The obtained data showed that in 82-84% of human breast tumors there is either downregulation or loss of D-glucuronyl C5-epimerase mRNA expression and significant decrease of the protein content. In most cases (77%), GLCE expression was decreased also in the normal-appearing tissue surrounding the tumor node but the protein amount was comparable to normal breast tissue. These findings represent the first data about involvement of human D-glucuronyl C5-epimerase in malignant transformation. PMID:17985344

Grigorieva, Elvira; Eshchenko, Tatiana; Rykova, Valentina I; Chernakov, Alexei; Zabarovsky, Eugene; Sidorov, Sergei V

2008-03-01

310

'Revertant' DCIS in human axillary breast carcinoma metastases.  

PubMed

Recent experimental evidence obtained in Scid mice has suggested that the metastatic process is in large part epigenetically regulated and undergoes partial reversion once the metastatic process is completed: the metastatic colonies become more engaged in the process of growing in situ than actively metastasizing. Based on this experimental evidence, examples were sought of metastatic human cancers where similar reversion to an in situ growth state was occurring. Review of 200 cases of metastatic human breast cancer revealed a 21 per cent incidence of reversion to a ductal carcinoma in situ (DCIS) growth pattern within axillary nodal metastases. The revertant DCIS areas were characterized by an intact and circumferential basement membrane, as demonstrated by extracellular laminin and type IV collagen immunoreactivity. These revertant DCIS areas could be distinguished from primary DCIS, however, by the absence of surrounding myoepithelial cells in the former, identified in the latter by their positive maspin, S-100, and smooth muscle actin immunoreactivity. The pattern of revertant DCIS, poorly differentiated (comedo) (13 per cent), intermediate (non-comedo) (6 per cent), or well-differentiated (non-comedo) (2%), exhibited complete 100 per cent concordance with the primary DCIS pattern. The concordance of histological patterns held true for even the subtypes of DCIS determined by architectural pattern, such as the micropapillary or cribriform subtypes. Nuclear size by digital image analysis and Her-2/neu, p53, and Ki-67 status in the revertant DCIS also exhibited complete concordance with the primary DCIS counterparts. Cases exhibiting a revertant DCIS pattern tended to be ER-negative/EGFR-positive and exhibited significant nodal involvement (mean number, 9; mean area, 90 per cent) compared with cases lacking a revertant pattern (mean number, 4; mean area, 15 per cent) (P < 0.01) These findings suggest that reversion of the metastatic phenotype may also be occurring within autochthonous human metastasis. PMID:9390032

Barsky, S H; Doberneck, S A; Sternlicht, M D; Grossman, D A; Love, S M

1997-10-01

311

Glypican-1 Is Overexpressed in Human Breast Cancer and Modulates the Mitogenic Effects of Multiple Heparin-binding Growth Factors in Breast Cancer Cells1  

Microsoft Academic Search

Glypicans are a family of glycosylphosphatidylinositol-anchored cell sur- face heparan sulfate proteoglycans implicated in the control of cellular growth and differentiation. Here we show that glypican-1 is strongly ex- pressed in human breast cancers, whereas expression of glypican-1 is low in normal breast tissues. In contrast, the expression of glypican-3 and -4 is only slightly increased in breast cancers by

Kei Matsuda; Haruhisa Maruyama; Fang Guo; Jorg Kleeff; Jun Itakura; Yoshiro Matsumoto; Arthur D. Lander; Murray Korc

2001-01-01

312

Fulvestrant-induced expression of ErbB3 and ErbB4 receptors sensitizes oestrogen receptor-positive breast cancer cells to heregulin ?1  

PubMed Central

Introduction We have previously reported that induction of epidermal growth factor receptor and ErbB2 in response to antihormonal agents may provide an early mechanism to allow breast cancer cells to evade the growth-inhibitory action of such therapies and ultimately drive resistant cell growth. More recently, the other two members of the ErbB receptor family, ErbB3 and ErbB4, have been implicated in antihormone resistance in breast cancer. In the present study, we have investigated whether induction of ErbB3 and/or ErbB4 may provide an alternative resistance mechanism to antihormonal action in a panel of four oestrogen receptor (ER)-positive breast cancer cell lines. Methods MCF-7, T47D, BT474 and MDAMB361 cell lines were exposed to fulvestrant (100 nM) for seven days, and effects on ErbB3/4 expression and signalling, as well as on cell growth, were assessed. Effects of heregulin ?1 (HRG?1) were also examined in the absence and presence of fulvestrant to determine the impact of ER blockade on the capacity of this ErbB3/4 ligand to promote signalling and cell proliferation. Results Fulvestrant potently reduced ER expression and transcriptional activity and significantly inhibited growth in MCF-7, T47D, BT474 and MDAMB361 cells. However, alongside this inhibitory activity, fulvestrant also consistently induced protein expression and activity of ErbB3 in MCF-7 and T47D cells and ErbB4 in BT474 and MDAMB361 cell lines. Consequently, fulvestrant treatment sensitised all cell lines to the actions of the ErbB3/4 ligand HRG?1 with enhanced ErbB3/4-driven signalling activity, reexpression of cyclin D1 and significant increases in cell proliferation being observed when compared to untreated cells. Indeed, in T47D and MDAMB361 HRG?1 was converted from a ligand having negligible or suppressive growth activity into one that potently promoted cell proliferation. Consequently, fulvestrant-mediated growth inhibition was completely overridden by HRG?1 in all four cell lines. Conclusions These findings suggest that although antihormones such as fulvestrant may have potent acute growth-inhibitory activity in ER-positive breast cancer cells, their ability to induce and sensitise cells to growth factors may serve to reduce and ultimately limit their inhibitory activity.

2011-01-01

313

Role of Basic Fibroblast Growth Factor in Human Breast Cancer.  

National Technical Information Service (NTIS)

Although basic fibroblast growth factor (bFGF) is a classical mitogen and survival factor in fibroblasts and endothelial cells, it inhibits proliferation in breast cancer cells. We investigated the survival effects of bFGF in MCF-7 breast cancer cells to ...

R. Wieder

1996-01-01

314

Cloning of Novel Oncogenes Involved in Human Breast Cancer.  

National Technical Information Service (NTIS)

The genetic determinants which lie behind the development of breast cancer remain largely uncharacterized. In order to identify genes which may play a role in breast cancer we have begun a process of manufacturing cDNA expression libraries derived from hu...

G. Clark

1998-01-01

315

Cloning of Novel Oncogenes Involved in Human Breast Cancer.  

National Technical Information Service (NTIS)

While the aberrant overexpression of HER family receptors is known to be involved in breast cancer, the complex nature of the genetic events that trigger the development of breast cancer remain to be identified. The authors have developed, refined, and ap...

C. J. Der

2002-01-01

316

Timing of Critical Genetic Changes in Human Breast Disease  

Microsoft Academic Search

Background: Breast cancer development has been characterized as a nonobligatory sequence of histological changes from normal epithelium through invasive malignancy. Although genetic alterations are thought to accumulate stochastically during tumorigenesis, little is known about the timing of critical mutations. This study examined allelic imbalance (AI) in tissue samples representing a continuum of breast cancer development to examine the evolution of

Rachel E. Ellsworth; Darrell L. Ellsworth; Brenda Deyarmin; Laurel R. Hoffman; Brad Love; Jeffrey A. Hooke; Craig D. Shriver

2005-01-01

317

Rapamycin sensitizes Akt inhibition in malignant human breast epithelial cells  

PubMed Central

Akt and mTOR are therapeutic targets for the treatment of cancer. The effects of inhibiting mTOR, with rapamycin, and Akt, with A-443654, concurrently, on cell morphology, cell proliferation, the cell cycle, and apoptosis were examined using the benign MCF10A and malignant MCF10CA1a human breast epithelial cells. Rapamycin and A-443654 in combination produced the greatest morphological changes and inhibited cell proliferation by G2/M arrest. Rapamycin and A-443654 in combination induced apoptosis at earlier times and at lower A-443654 concentrations in MCF10CA1a tumor cells than in the benign MCF10A cells. Rapamycin and A-443654 increased p53 and p15INK4B protein levels, decreased anti-apoptotic Bcl-2 levels, and increased Bad levels in the MCF10CA1a tumor cells by ~ 5-fold. These results suggest that the combined inhibition of Akt and mTOR may have beneficial therapeutic and safety margin effects.

Zheng, Jie; Hudder, Alice; Zukowski, Kim; Novak, Raymond F.

2010-01-01

318

Phorbol esters induce multidrug resistance in human breast cancer cells  

SciTech Connect

Mechanisms responsible for broad-based resistance to antitumor drugs derived from natural products (multidrug resistance) are incompletely understood. Agents known to reverse the multidrug-resistant phenotype (verapamil and trifluoperazine) can also inhibit the activity of protein kinase C. When the authors assayed human breast cancer cell lines for protein kinase C activity, they found that enzyme activity was 7-fold higher in the multidrug-resistance cancer cells compared with the control, sensitive parent cells. Exposure of drug-sensitive cells to the phorbol ester phorbol 12,13-dibutyate (P(BtO)/sub 2/) led to an increase in protein kinase C activity and induced a drug-resistance phenotype, whereas exposure of drug-resistant cells to P(BtO)/sub 2/ further increased drug resistance. In sensitive cells, this increased resistance was accomplished by a 3.5-fold increased phosphorylation of a 20-kDa particulate protein and a 35-40% decreased intracellular accumulation of doxorubicin and vincristine. P(BtO)/sub 2/ induced resistance to agents involved in the multidrug-resistant phenotype (doxorubicin and vincristine) but did not affect sensitivity to an unrelated alkylating agent (melphalan). The increased resistance was partially or fully reversible by the calcium channel blocker verapamil and by the calmodulin-antagonist trifluoperazine. These data suggest that stimulation of protein kinase C playus a role in the drug-transport changes in multidrug-resistant cells. This may occur through modulation of an efflux pump by protein phosphorylation.

Fine, R.L.; Patel, J.; Chabner, B.A.

1988-01-01

319

Polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls levels in human breast milk from different regions of Turkey  

Microsoft Academic Search

Human breast milk offers the optimal nutrition for all infants and have been widely used in biomonitoring programs to assess human exposure to lipophylic environmental contaminants such as polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCB). There are no previous reports from Turkey on chemically determined levels of PCDDs, PCDFs, and PCBs in human breast milk expressed as

Ismet Çok; Menekse Keski Donmez; Mine Uner; Erkan Demirkaya; Bernhard Henkelmann; Heqing Shen; Jarmila Kotalik; Karl-Werner Schramm

2009-01-01

320

Hormone Receptor and ERBB2 Status in Gene Expression Profiles of Human Breast Tumor Samples  

PubMed Central

The occurrence of large publically available repositories of human breast tumor gene expression profiles provides an important resource to discover new breast cancer biomarkers and therapeutic targets. For example, knowledge of the expression of the estrogen and progesterone hormone receptors (ER and PR), and that of the ERBB2 in breast tumor samples enables choice of therapies for the breast cancer patients that express these proteins. Identifying new biomarkers and therapeutic agents affecting the activity of signaling pathways regulated by the hormone receptors or ERBB2 might be accelerated by knowledge of their expression levels in large gene expression profiling data sets. Unfortunately, the status of these receptors is not invariably reported in public databases of breast tumor gene expression profiles. Attempts have been made to employ a single probe set to identify ER, PR and ERBB2 status, but the specificity or sensitivity of their prediction is low. We enquired whether estimation of ER, PR and ERBB2 status of profiled tumor samples could be improved by using multiple probe sets representing these three genes and others with related expression. We used 8 independent datasets of human breast tumor samples to define gene expression signatures comprising 24, 51 and 14 genes predictive of ER, PR and ERBB2 status respectively. These signatures, as demonstrated by sensitivity and specificity measures, reliably identified hormone receptor and ERBB2 expression in breast tumors that had been previously determined using protein and DNA based assays. Our findings demonstrate that gene signatures can be identified which reliably predict the expression status of the estrogen and progesterone hormone receptors and that of ERBB2 in publically available gene expression profiles of breast tumor samples. Using these signatures to query transcript profiles of breast tumor specimens may enable discovery of new biomarkers and therapeutic targets for particular subtypes of breast cancer.

Dvorkin-Gheva, Anna; Hassell, John A.

2011-01-01

321

Fibroblast activation protein expression by stromal cells and tumor-associated macrophages in human breast cancer.  

PubMed

Fibroblast activation protein (FAP) has long been known to be expressed in the stroma of breast cancer. However, very little is known if the magnitude of FAP expression within the stroma may have a prognostic value and reflect the heterogeneous biology of the tumor cell. An earlier study had suggested that stromal FAP expression in breast cancer was inversely proportional to prognosis. We, therefore, hypothesized that stromal FAP expression may correlate with clinicopathologic variables and may serve as an adjunct prognostic factor in breast cancer. We evaluated the expression of FAP in a panel of breast cancer tissues (n = 52) using a combination of immunostain analyses at the tissue and single-cell level using freshly frozen or freshly digested human breast tumor samples, respectively. Our results showed that FAP expression was abundantly expressed in the stroma across all breast cancer subtypes without significant correlation with clinicopathologic factors. We further identified a subset of FAP-positive (or FAP(+)) stromal cells that also expressed CD45, a pan-leukocyte marker. Using freshly dissociated human breast tumor specimens (n = 5), we demonstrated that some of these FAP(+)CD45(+) cells were CD11b(+)CD14(+)MHC-II(+), indicating that they were likely tumor-associated macrophages (TAMs). Although FAP(+)CD45(+) cells have been demonstrated in the mouse tumor stroma, our results demonstrating that human breast TAMs expressed FAP were novel and suggested that existing and future FAP-directed therapy may have dual-therapeutic benefits targeting both stromal mesenchymal cells and immune cells such as TAMs. More work is needed to explore the role of FAP as a potential targetable molecule in breast cancer treatment. PMID:24074532

Tchou, Julia; Zhang, Paul J; Bi, Yingtao; Satija, Celine; Marjumdar, Rajrupa; Stephen, Tom L; Lo, Albert; Chen, Haiying; Mies, Carolyn; June, Carl H; Conejo-Garcia, Jose; Puré, Ellen

2013-09-26

322

Tumor-infiltrating ?? T lymphocytes predict clinical outcome in human breast cancer.  

PubMed

Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of ?? regulatory T cells have been discovered in breast TILs. However, the clinical relevance of these intratumoral ?? T cells is unknown. In this study, ?? T cell populations were analyzed by performing immunohistochemical staining in primary breast cancer tissues from patients with different stages of cancer progression. Retrospective multivariate analyses of the correlations between ?? T cell levels and other prognostic factors and clinical outcomes were completed. We found that ?? T cell infiltration and accumulation in breast tumor sites was a general feature in breast cancer patients. Intratumoral ?? T cell numbers were positively correlated with advanced tumor stages, HER2 expression status, and high lymph node metastasis but inversely correlated with relapse-free survival and overall survival of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating ?? T cells and other prognostic factors further suggested that intratumoral ?? T cells represented the most significant independent prognostic factor for assessing severity of breast cancer compared with the other known factors. Intratumoral ?? T cells were positively correlated with FOXP3(+) cells and CD4(+) T cells but negatively correlated with CD8(+) T cells in breast cancer tissues. These findings suggest that intratumoral ?? T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer. PMID:23034170

Ma, Chunling; Zhang, Qunyuan; Ye, Jian; Wang, Fang; Zhang, Yanping; Wevers, Eric; Schwartz, Theresa; Hunborg, Pamela; Varvares, Mark A; Hoft, Daniel F; Hsueh, Eddy C; Peng, Guangyong

2012-10-03

323

Regression of Human Breast Carcinoma Tumors in Immunodeficient Mice Treated with 9-Nitrocamptothecin: Differential Response of Nontumorigenic and Tumorigenic Human Breast Cells in Vitro1  

Microsoft Academic Search

We have shown recently that the plant alkaloid camptothecin and its derivatives inhibited growth of human carcinoma and melanoma cells in vitro and induced regression of advanced human malignant melanoma tumors growing in immunodeficient (nude) mice. Here, we have extended these studies to show that the camptothecin derivative 9-nitro-20(S)-camp- tothecin (9NC) induces complete regression of advanced breast carcinoma tumors growing

Panayotis Pantazis; Janet A. Early; Anthony J. Kozielski; John T. Mendoza; Hellmuth R. Hinz; Beppino C. Giovanella

1993-01-01

324

Quantification of naturally occurring benzodiazepine-like substances in human breast milk  

Microsoft Academic Search

The possible occurrence of benzodiazepine-like substances in human breast milk was investigated in 35 healthy, newly delivered women who were known not to be taking benzodiazepines. Maternal blood samples and a sample of breast milk were obtained on the fifth post partum day. A radioreceptor technique (lower limit of detection 1.5 ng\\/ml; difference between duplicates at various concentrations <7%) was

Sven J. Dencker; Gunvor Johansson; Ian Milsom

1992-01-01

325

A new diploid nontumorigenic human breast epithelial cell line isolated and propagated in chemically defined medium  

Microsoft Academic Search

Summary  A new, nontumorigenic human breast epithelial cell line, HMT-3522, has been established from fibrocystic breast tissue. Cells\\u000a were explanted and propagated in chemically defined medium including insulin, transferrin, epidermal growth factor, hydrocortisone,\\u000a estradiol, prolactin, and Na-selenite. The epithelial nature of the cell line was established by immunocytochemical detection\\u000a of cytokeratins. Moreover, electronmicroscopy revealed monolayers of polarized cells connected by desmosomes

P. Briand; O. W. Petersen; B. Van Deurs

1987-01-01

326

Clotrimazole Preferentially Inhibits Human Breast Cancer Cell Proliferation, Viability and Glycolysis  

Microsoft Academic Search

BackgroundClotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of glycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to analyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles.Methodology\\/Principal FindingsThree cell lines derived from human breast tissue

Cristiane M. Furtado; Mariah C. Marcondes; Mauro Sola-Penna; Maisa L. S. de Souza; Patricia Zancan

2012-01-01

327

Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction  

Microsoft Academic Search

The aim of this study was to determine the mechanisms of curcumin-induced human breast cancer cell apoptosis. From quantitative image analysis data showing an increase in the percentage of cells with a sub-G0\\/G1 DNA content, we demonstrated curcumin-induced apoptosis in the breast cancer cell line MCF-7, in which expression of wild-type p53 could be induced. Apoptosis was accompanied by an

Tathagata Choudhuri; Suman Pal; Munna L Agwarwal; Tanya Das; Gaurisankar Sa

2002-01-01

328

Expression and regulation of Cyr61 in human breast cancer cell lines  

Microsoft Academic Search

We have shown that Cyr61, an angiogenic regulator, is overexpressed in invasive and metastatic human breast cancer cells and tumor biopsies. We have further demonstrated that Cyr61 promotes acquisition of estrogen-independence and anti-estrogen resistance in vivo in breast cancer cells. Moreover, we have demonstrated that Cyr61 induces tumor formation and tumor vascularization in vivo, events mediated through the activation of

Miaw-Sheue Tsai; Daphne F Bogart; Patricia Li; Inderjit Mehmi; Ruth Lupu

2002-01-01

329

Excretion of Granulocyte Colony-Stimulating Factor into Human Breast Milk  

Microsoft Academic Search

Excretion of human recombinant granulocyte colony-stimulating factor (G-CSF) into milk is reportedly low in rats, but is undetermined in humans [1–3]. We measured concentrations of G-CSF in human breast milk, obtained from a healthy breastfeeding mother, and found that G-CSF was excreted into human milk. A healthy 30-year-old woman was admitted on August 23, 2002, as the peripheral blood stem

Hisako Shibata; Takahisa Yamane; Yasutaka Aoyama; Hirohisa Nakamae; Taro Hasegawa; Chikahiko Sakamoto; Yoshiki Terada; Genju Koh; Masayuki Hino

2003-01-01

330

Prognostic role of p27Kip1 and apoptosis in human breast cancer  

PubMed Central

Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from an indolent slowly progressive one to a course associated with rapid progression and metastatic spread. It is important to establish prognostic factors which will define subgroups of patients with low vs high risk of recurrence so as to better define the need for additional therapy. Additional characterization of the molecular make-up of breast cancer phenotypes should provide important insights into the biology of breast cancer. In the present study, we investigated apoptosis, expression of p27Kip1 and p53 retrospectively in 181 human breast cancer specimens. In addition, their relevance to the biological behaviour of breast cancer was examined. Our studies found a significant association among high histological grade, high p53, low apoptosis and low p27. Our results also demonstrated that, in human breast cancer, low levels of p27 and apoptotic index (AI) strongly correlated with the presence of lymph node metastasis and decreased patient survival. In node-negative patients, however, p27 also had prognostic value for relapse-free and overall survival in multivariate analysis. Furthermore p27 and AI had predictive value for the benefits of chemotherapy. These latter observations should prompt prospective randomized studies designed to investigate the predictive role of p27 and AI in determining who should receive chemotherapy in node-negative patients. © 1999 Cancer Research Campaign

Wu, J; Shen, Z-Z; Lu, J-S; Jiang, M; Han, Q-X; Fontana, J A; Barsky, S H; Shao, Z-M

1999-01-01

331

Selection of Human Antibody Fragments which Bind Novel Breast Tumor Antigens.  

National Technical Information Service (NTIS)

This report describes the results of year 1 of a 4 year grant to develop high affinity human antibody fragments to novel breast tumor antigens. To produce human antibody fragments which bind to novel tumor antigens, we have created a very large (7.0 x mem...

J. D. Marks

1995-01-01

332

A novel assay to assess the effectiveness of antiangiogenic drugs in human breast cancer.  

Technology Transfer Automated Retrieval System (TEKTRAN)

Many cytotoxic drugs maintain antiangiogenic properties, but there are no human, tumor-based assays to evaluate their antiangiogenic potential. We used a fibrin-thrombin clot-based angiogenesis model to evaluate the angiogenic response of human breast cancer to various cytotoxic agents commonly used...

333

Urinary melatonin levels in human breast cancer patients  

Microsoft Academic Search

Summary Urinary melatonin levels were measured in 10 postmenopausal Indian women suffering from advanced stages of breast cancer and in 9 well-matched women with non-endocrine complaints, mostly uterovaginal prolapse.

C. Bartsch; Hella Bartsch; A. K. Jain; K. R. Laumas; L. Wetterberg

1981-01-01

334

Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: correlation with clinicopathologic parameters.  

PubMed

The polyamines putrescine, spermidine, and spermine and ornithine decarboxylase (ODC), the rate-limiting enzyme in their biosynthetic pathway, play an important role in cell proliferation, differentiation, and transformation. In the present study, we have analyzed polyamine concentrations and ODC activity in samples from benign breast diseases (n = 36), benign breast tissue adjacent to the primary carcinoma (n = 19), and breast carcinoma (n = 104). ODC activity in primary carcinoma was significantly higher (2.42 +/- 0.22 nmol CO2/h g; P < 0.001) than that found in benign breast (0.62 +/- 0.15 nmol CO2/h g) or in breast tissue adjacent to the primary carcinoma (0.52 +/- 0.16 nmol CO2/h g). The total polyamine content of breast cancer tissues was higher than in benign breast diseases (704.3 +/- 38.3 nmol/g wet weight versus 295.8 +/- 27.4 nmol/g wet weight) and correlated well with ODC activity (Pearson, r = 0.42; P < 0.001). ODC activity correlated with histological grade, peritumoral lymphatic or blood vessel invasion, S-phase fraction, and cathepsin D. Total polyamine concentration increased with S-phase fraction, cathepsin D, and aneuploidy. No significant correlation was found between ODC or polyamines and tumor size, lymph node involvement, or steroid receptor status. A major finding in our study was that ODC activity was an independent prognostic factor for recurrence and death. The results indicate that the estimation of ODC activity and polyamines in human breast carcinoma might be useful to determine tumor aggressiveness and suggest that ODC may have a potential value as both a prognostic factor and a chemoprevention target in human breast cancer. PMID:10473083

Cañizares, F; Salinas, J; de las Heras, M; Diaz, J; Tovar, I; Martinez, P; Peñafiel, R

1999-08-01

335

MDA-MB-435 human breast carcinoma metastasis to bone  

Microsoft Academic Search

Breast cancer metastasizes to bone with high frequency and incidence. However, studies of breast cancer metastasis to bone\\u000a have been limited by two factors. First, the number of models that colonize bone are limited. Second, detection of bone metastases\\u000a is too insensitive or too laborious for routine, large-scale studies or for studying the earliest steps in bone colonization.\\u000a To partially

John F. Harms; Danny R. Welch

2003-01-01

336

EVIDENCE FOR THE PRESENCE OF MUTAGENIC ARYL AMINES IN HUMAN BREAST MILK AND DNA ADDUCTS IN EXFOLIATED BREAST-DUCT EPITHELIAL CELLS  

EPA Science Inventory

Aromatic (AA) and heterocyclic amines (HAA) are ubiquitous environmental mutagens present in combustions emissions, fried meats, tobacco smoke, etc., and are suspect human mammary carcinogens. To determine the presence of aryl amines in breast tissue and fluid, we examined exfol...

337

Estrogen Up-regulates Neuropeptide Y Y1 Receptor Expression in a Human Breast Cancer Cell Line  

Microsoft Academic Search

Normal breast tissue mainly expresses the neuropeptide Y (NPY) Y2 receptor whereas primary human breast carcinomas express the Y1 receptor (Y1R) subtype. We hypothesized that activation ofestrogen signaling systems plays a role in the induction ofY1R. To investigate this possibility, we used estrogen receptor-positive (ER+) human breast carcinoma cell line, MCF-7, and examined the effect of estrogen on Y1R gene

Hassane Amlal; Somia Faroqui; Ambikaipakan Balasubramaniam

338

Transforming Growth Factor ß: Potential Autocrine Growth Inhibitor of Estrogen Receptor-negative Human Breast Cancer Cells1  

Microsoft Academic Search

Transforming growth factor ß (TGF0), a two-subunit M, 25,000 poh - peptide, inhibits growth of several epithelial human cancer cell lines and has been proposed as an autocrine growth inhibitor. IGF\\/3 activity has been found in conditioned media from some breast cancer cell lines, and TGF\\/3 niR.NAhas been detected in breast cancer cell lines and human breast cancer specimens. In

Carlos L. Arteaga; Atul K. Tandon; Daniel D. Von Hoff; C. Kent Osborne

1988-01-01

339

Prolactin-induced protein (PIP) regulates proliferation of luminal A type breast cancer cells in an estrogen-independent manner.  

PubMed

Prolactin-induced Protein (PIP), an aspartyl protease unessential for normal mammalian cell function, is required for the proliferation and invasion of some breast cancer (BCa) cell types. Because PIP expression is particularly high in the Luminal A BCa subtype, we investigated the roles of PIP in the related T47D BCa cell line. Nucleic acid and antibody arrays were employed to screen effects of PIP silencing on global gene expression and activation of receptor tyrosine kinases (RTKs), respectively. Expression of PIP-stimulated genes, as defined in the T47D cell culture model, was well correlated with the expression of PIP itself across a cohort of 557 mRNA profiles of diverse BCa tumors, and bioinformatics analysis revealed cJUN and cMYC as major nodes in the PIP-dependent gene network. Among 71 RTKs tested, PIP silencing resulted in decreased phosphorylation of focal adhesion kinase (FAK), ephrin B3 (EphB3), FYN, and hemopoietic cell kinase (HCK). Ablation of PIP also abrogated serum-induced activation of the downstream serine/threonine kinases AKT, ERK1/2, and JNK1. Consistent with these results, PIP-depleted cells exhibited defects in adhesion to fibronectin, cytoskeletal stress fiber assembly and protein secretion. In addition, PIP silencing abrogated the mitogenic response of T47D BCa cells to estradiol (E2). The dependence of BCa cell proliferation was unrelated, however, to estrogen signaling because: 1) PIP silencing did not affect the transcriptional response of estrogen target genes to hormone treatment, and 2) PIP was required for the proliferation of tamoxifen-resistant BCa cells. Pharmacological inhibition of PIP may therefore serve the bases for both augmentation of existing therapies for hormone-dependent tumors and the development of novel therapeutic approaches for hormone-resistant BCa. PMID:23755096

Baniwal, Sanjeev K; Chimge, Nyam-Osor; Jordan, V Craig; Tripathy, Debu; Frenkel, Baruch

2013-06-03

340

DNA Replication Licensing and Progenitor Numbers Are Increased by Progesterone in Normal Human Breast  

PubMed Central

Proliferation in the nonpregnant human breast is highest in the luteal phase of the menstrual cycle when serum progesterone levels are high, and exposure to progesterone analogues in hormone replacement therapy is known to elevate breast cancer risk, yet the proliferative effects of progesterone in the human breast are poorly understood. In a model of normal human breast, we have shown that progesterone increased incorporation of 5-bromo-2?-deoxyuridine and increased cell numbers by activation of pathways involved in DNA replication licensing, including E2F transcription factors, chromatin licensing and DNA replication factor 1 (Cdt1), and the minichromosome maintenance proteins and by increased expression of proteins involved in kinetochore formation including Ras-related nuclear protein (Ran) and regulation of chromosome condensation 1 (RCC1). Progenitor cells competent to give rise to both myoepithelial and luminal epithelial cells were increased by progesterone, showing that progesterone influences epithelial cell lineage differentiation. Therefore, we have demonstrated that progesterone augments proliferation of normal human breast cells by both activating DNA replication licensing and kinetochore formation and increasing bipotent progenitor numbers.

Graham, J. Dinny; Mote, Patricia A.; Salagame, Usha; van Dijk, Jessica H.; Balleine, Rosemary L.; Huschtscha, Lily I.; Reddel, Roger R.; Clarke, Christine L.

2009-01-01

341

Skp2 Regulates Subcellular Localization of PPAR? by MEK Signaling Pathways in Human Breast Cancer  

PubMed Central

Nuclear hormone receptor family member PPAR? plays an important role in mammary gland tumorigenesis. Previous studies have shown PPAR? has cytoplasmic activities upon tetradecanoyl phorbol acetate (TPA) stimulation. However, the clinical pathological significance of cytoplasmic PPAR? is not completely understood in human breast cancer. Skp2 is oncogenic, and its frequent amplification and overexpression correlated with the grade of malignancy. In this study, the role of cytoplasmic PPAR? and Skp2 expression was investigated in human breast cancer progression. Therefore, immunohistochemical analysis was performed on formalin-fixed paraffin sections of 70 specimens. Furthermore, Western blot and immunofluorescence microscopy analysis were used to study the relationship between expression of cytoplasmic PPAR? and Skp2 expression in human breast cancer cells in vitro. Results showed that the expression of cytoplasmic PPAR? was positively correlated with Skp2 expression (p < 0.05), and correlated significantly with estrogen receptor (p = 0.026) and pathological grade (p = 0.029), respectively. In addition, Skp2 overexpression can provoke cytoplasmic localization of PPAR? upon MEK1-dependent mechanisms in human breast cancer cells by nuclear-cytosolic fractionation technology and immunofluorescence microscopy analysis. Using RNA interference technology, we also found that down-regulated Skp2 reduced the phosphorylation level of MEK1 and significantly reversed TPA-induced nuclear export of PPAR? in MDA-MB-231 cells. The changes in the subcellular localization of PPAR? may represent a novel target for selective interference in patients with breast cancer.

Cheng, Hongge; Meng, Jie; Wang, Guisheng; Meng, Yuming; Li, Yu; Wei, Dong; Fu, Chunyun; Deng, Kaifeng; Shen, Aiguo; Wang, Huimin; Dai, Shengming

2013-01-01

342

Nuclear localization and cytosolic overexpression of LASP-1 correlates with tumor size and nodal-positivity of human breast carcinoma  

Microsoft Academic Search

BACKGROUND: LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration, which was reported to be overexpressed in 8–12 % of human breast cancers and thought to be exclusively located in cytoplasm. METHODS: In the present work we analyzed the cellular and histological expression pattern of

Thomas GP Grunewald; Ulrike Kammerer; Michaela Kapp; Matthias Eck; Johannes Dietl; Elke Butt; Arnd Honig

2007-01-01

343

Adiponectin, Adipocyte Fatty Acid Binding Protein, and Epidermal Fatty Acid Binding Protein: Proteins Newly Identified in Human Breast Milk  

Microsoft Academic Search

Background: Breastfeeding may protect children from developing metabolic syndrome and other diseases later in life. We investigated novel proteins in human breast milk that might play a role in this process. Methods: We used ELISA to measure adiponectin, adi- pocyte and epidermal fatty acid binding proteins (AFABP, EFABP) and leptin concentrations in human breast milk obtained from 59 mothers 48

Michal Karpisek; Eva Bronska; Marta Pechova

2006-01-01

344

Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles  

Microsoft Academic Search

BACKGROUND: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression

Robert Klopfleisch; Dido Lenze; Michael Hummel; Achim D Gruber

2010-01-01

345

Cytotoxicity of the organic ruthenium anticancer drug Nami-A is correlated with DNA binding in four different human tumor cell lines  

Microsoft Academic Search

Purpose The cytotoxicity, intracellular accumulation and DNA adduct formation of the ruthenium complex imidazolium trans-imidazoledimethylsulfoxide tetrachlororuthenate (ImH[ trans-RuCl 4(DMSO)Im], Nami-A) were compared in vitro with those of cisplatin in four human tumor cell lines: Igrov-1, 2008, MCF-7, and T47D. Methods Cytotoxicity was assessed in vitro using a growth inhibition assay. Accumulation was determined by flameless atomic absorption spectroscopy (AAS). GG

Dick Pluim; Robert C. A. M. van Waardenburg; Jos H. Beijnen; Jan H. M. Schellens

2004-01-01

346

MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype  

PubMed Central

Background MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression. Results Here we report the analysis of miRNA expression in 93 primary human breast tumors, using a bead-based flow cytometric miRNA expression profiling method. Of 309 human miRNAs assayed, we identify 133 miRNAs expressed in human breast and breast tumors. We used mRNA expression profiling to classify the breast tumors as luminal A, luminal B, basal-like, HER2+ and normal-like. A number of miRNAs are differentially expressed between these molecular tumor subtypes and individual miRNAs are associated with clinicopathological factors. Furthermore, we find that miRNAs could classify basal versus luminal tumor subtypes in an independent data set. In some cases, changes in miRNA expression correlate with genomic loss or gain; in others, changes in miRNA expression are likely due to changes in primary transcription and or miRNA biogenesis. Finally, the expression of DICER1 and AGO2 is correlated with tumor subtype and may explain some of the changes in miRNA expression observed. Conclusion This study represents the first integrated analysis of miRNA expression, mRNA expression and genomic changes in human breast cancer and may serve as a basis for functional studies of the role of miRNAs in the etiology of breast cancer. Furthermore, we demonstrate that bead-based flow cytometric miRNA expression profiling might be a suitable platform to classify breast cancer into prognostic molecular subtypes.

Blenkiron, Cherie; Goldstein, Leonard D; Thorne, Natalie P; Spiteri, Inmaculada; Chin, Suet-Feung; Dunning, Mark J; Barbosa-Morais, Nuno L; Teschendorff, Andrew E; Green, Andrew R; Ellis, Ian O; Tavare, Simon; Caldas, Carlos; Miska, Eric A

2007-01-01

347

The differential processing of proenkephalin A in mouse and human breast tumour cell lines.  

PubMed

We have carried out an investigation into the processing of the enkephalin-like immunoreactivity reported in breast tissue using two human breast tumour cell lines and a mouse tumour cell line. A 46 kDa form of proenkephalin (PE) has been observed in the cell lysates of two human breast tumour cell lines (MCF-7, ZR-75-1) and the mouse androgen-responsive Shionogi breast carcinoma cell line (SC115). PE processing in the cell lysates of these cells was assessed by a specific met-enkephalin RIA. The basal levels of processed PE in the MCF-7, ZR-75-1 and SC115 cell lysates were 30, 30 and 76% respectively. The processing enzymes PC1 and PC2, which have been implicated in the differential processing of PE, were detected by immunoblot analysis in these cells. PC1 was found within the cell extracts of all three cell lines. PC2 was only observed in the SC115 cell line, which may account for the higher percentage of processed PE measured. The cDNA of PC2 has been transfected into ZR-75-1 cells and this was accompanied by an increase in the level of processed PE from 30 to 76%. These breast tumour cell lines may provide a useful insight into the function of enkephalin-containing peptides in breast cancer. PMID:10333550

Brar, B K; Lowry, P J

1999-06-01

348

A New Mouse Model for the Study of Human Breast Cancer Metastasis  

PubMed Central

Breast cancer is the most common cancer in women, and this prevalence has a major impact on health worldwide. Localized breast cancer has an excellent prognosis, with a 5-year relative survival rate of 85%. However, the survival rate drops to only 23% for women with distant metastases. To date, the study of breast cancer metastasis has been hampered by a lack of reliable metastatic models. Here we describe a novel in vivo model using human breast cancer xenografts in NOD scid gamma (NSG) mice; in this model human breast cancer cells reliably metastasize to distant organs from primary tumors grown within the mammary fat pad. This model enables the study of the entire metastatic process from the proper anatomical site, providing an important new approach to examine the mechanisms underlying breast cancer metastasis. We used this model to identify gene expression changes that occur at metastatic sites relative to the primary mammary fat pad tumor. By comparing multiple metastatic sites and independent cell lines, we have identified several gene expression changes that may be important for tumor growth at distant sites.

Iorns, Elizabeth; Drews-Elger, Katherine; Ward, Toby M.; Dean, Sonja; Clarke, Jennifer; Berry, Deborah; Ashry, Dorraya El; Lippman, Marc

2012-01-01

349

Combined photoacoustic and acoustic imaging of human breast specimens in the mammographic geometry.  

PubMed

A photoacoustic volume imaging (PAVI) system was designed to study breast cancer detection and diagnosis in the mammographic geometry in combination with automated 3-D ultrasound (AUS). The goal of the work described here was to validate the design and evaluate its performance in human breast tissues for non-invasive imaging of deeply positioned structures covering such geometry. The good penetration of near-infrared light and high receiving sensitivity of a broad-bandwidth, 572-element, 2-D polyvinylidene fluoride (PVDF) array at a low center frequency of 1 MHz were used with 20 channel simultaneous acquisition. Pseudo-lesions filled with dilute blood were imaged in three human breast specimens at various depths up to 49 mm. With near-infrared light illumination and 256-sample averaging, the extrapolated maximum depth in imaging a 2.4-mm blood-rich lesion with a 3-dB contrast-to-noise ratio in a compressed breast was 54 mm. Three-dimensional photoacoustic volume image stacks of the breasts were co-registered with 3-D ultrasound image stacks, suggesting for the first time that PAVI, based on the intrinsic tissue contrast, can visualize tissue interfaces other than those with blood, including the inner skin surface and connective tissue sheets. With the designed system, PAVI revealed satisfactory imaging depth and sensitivity for coverage of the entire breast when imaged from both sides in the mammographic geometry with mild compression. PMID:23972486

Xie, Zhixing; Hooi, Fong Ming; Fowlkes, J Brian; Pinsky, Renee W; Wang, Xueding; Carson, Paul L

2013-08-22

350

Paracrine Wnt signaling both promotes and inhibits human breast tumor growth  

PubMed Central

Wnt signaling in mouse mammary development and tumorigenesis has been heavily studied and characterized, but its role in human breast cancer remains elusive. Although Wnt inhibitors are in early clinical development, it is unclear whether they will be of therapeutic benefit to breast cancer patients, and subsequently, to which ones. To address this, we generated a panel of Wnt reporting human breast cancer cell lines and identified a previously unrecognized enrichment for the ability to respond to Wnt in the basal B or claudin-low subtype, which has a poor prognosis and no available targeted therapies. By co-injecting Wnt3A expressing human mammary fibroblasts with human breast cancer cell lines into mouse mammary fat pads, we showed that elevated paracrine Wnt signaling was correlated with accelerated tumor growth. Using this heterotypic system and a dual lentiviral reporter system that enables simultaneous real-time measurement of both Wnt-responsive cells and bulk tumor cells, we analyzed the outcome of elevated Wnt signaling in patient-derived xenograft (PDX) models. Interestingly, the PDX models exhibited responses not observed in the cell lines analyzed. Exogenous WNT3A promoted tumor growth in one human epidermal growth factor receptor 2-overexpressing PDX line but inhibited growth in a second PDX line obtained from a patient with triple-negative breast cancer. Tumor suppression was associated with squamous differentiation in the latter. Thus, our work suggests that paracrine Wnt signaling can either fuel or repress the growth of human breast cancers depending on yet to be determined aspects of the molecular pathways they express.

Green, Jennifer L.; La, Justin; Yum, Kyu W.; Desai, Payal; Rodewald, Luo-Wei; Zhang, Xiaomei; Leblanc, Mathias; Nusse, Roeland; Lewis, Michael T.; Wahl, Geoffrey M.

2013-01-01

351

Activation of rapid oestrogen signalling in aggressive human breast cancers  

PubMed Central

Oestrogen receptors can mediate rapid activation of cytoplasmic signalling cascades by recruiting Src and PI3K. However, the involvement of this pathway in breast cancer remains poorly defined. We have previously shown that methylation of ER? is required for the formation of the ER?/Src/PI3K complex and that ER? is hypermethylated in a subset of breast cancers. Here, we used Proximity Ligation Assay to demonstrate that this complex is present in the cytoplasm of breast cancer cell lines as well as formalin-fixed, paraffin-embedded tumours. Of particular interest, the analysis of 175 breast tumours showed that overexpression of this complex in a subset of breast tumours correlates to the activation of the downstream effector Akt. Survival analysis revealed that high expression of this complex is an independent marker of poor prognosis and associated with reduced disease-free survival. Our data introduces the new concept that the rapid oestrogen pathway is operative in vivo. It also provides a rationale for patient stratification defined by the activation of this pathway and the identification of target therapies.

Poulard, Coralie; Treilleux, Isabelle; Lavergne, Emilie; Bouchekioua-Bouzaghou, Katia; Goddard-Leon, Sophie; Chabaud, Sylvie; Tredan, Olivier; Corbo, Laura; Le Romancer, Muriel

2012-01-01

352

Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors  

Microsoft Academic Search

Background  Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully\\u000a represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles\\u000a from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors.\\u000a \\u000a \\u000a \\u000a \\u000a Results  Unsupervised hierarchical clustering analysis showed

Jason I Herschkowitz; Karl Simin; Victor J Weigman; Igor Mikaelian; Jerry Usary; Zhiyuan Hu; Karen E Rasmussen; Laundette P Jones; Shahin Assefnia; Subhashini Chandrasekharan; Michael G Backlund; Yuzhi Yin; Andrey I Khramtsov; Roy Bastein; John Quackenbush; Robert I Glazer; Powel H Brown; Jeffrey E Green; Levy Kopelovich; Priscilla A Furth; Juan P Palazzo; Olufunmilayo I Olopade; Philip S Bernard; Gary A Churchill; Terry Van Dyke; Charles M Perou

2007-01-01

353

Roles and Regulation of Stat Family Transcription Factors in Human Breast Cancer  

PubMed Central

Stats (for signal transducers and activators of transcription) are a family of transcription factors that regulate cell growth and differentiation. Their activity is latent until phosphorylation by receptor-associated kinases. A sizable body of data from cell lines, mouse models, and human tissues now implicates these transcription factors in the oncogenesis of breast cancer. Because Stat activity is modulated by several posttranslational modifications and protein-protein interactions, these transcription factors are capable of integrating inputs from multiple signaling networks. Given this, the future utilization of Stats as prognostic markers and therapeutic targets in human breast cancer appears likely.

Clevenger, Charles V.

2004-01-01

354

Temperature dependence of the magnetic volume susceptibility of human breast fat tissue: an NMR study  

Microsoft Academic Search

Object  Proton resonance frequency shift (PRFS)-based MR thermometry (MRT) is hampered by heat-induced susceptibility changes when\\u000a applied in tissues containing fat, e.g., the human breast. In order to assess the impact of fat susceptibility changes on\\u000a PRFS-based MRT during thermal therapy in the human breast, reliable knowledge of the temperature dependence of the magnetic\\u000a volume susceptibility of fat, d?fat\\/dT, is a

Sara M. Sprinkhuizen; Chris J. G. Bakker; Johannes H. Ippel; Rolf Boelens; Max A. Viergever; Lambertus W. Bartels

2012-01-01

355

Human Endogenous Retrovirus K Triggers an Antigen-Specific Immune Response in Breast Cancer Patients  

Microsoft Academic Search

Recent evidence indicates that human cancer cells reactivate the expression of latent human endogenous retroviral (HERV) proteins. However, the extent to which cancer patients mount de novo immune responses against expressed HERV elements is unclear. In this study, we determined the extent of HERV-K env expression in human breast cancer (BC) and whether both humoral and cell-mediated immunity against HERV-K

Laszlo Radvanyi; Kiera Rycaj; Joshua B. Plummer; Peisha Yan; Chandrika J. Piyathilake; Gary L. Johanning

356

Septin 9 isoform expression, localization and epigenetic changes during human and mouse breast cancer progression  

PubMed Central

Introduction Altered expression of Septin 9 (SEPT9), a septin coding for multiple isoform variants, has been observed in several carcinomas, including colorectal, head and neck, ovarian and breast, compared to normal tissues. The mechanisms regulating its expression during tumor initiation and progression in vivo and the oncogenic function of its different isoforms remain elusive. Methods Using an integrative approach, we investigated SEPT9 at the genetic, epigenetic, mRNA and protein levels in breast cancer. We analyzed a panel of breast cancer cell lines, human primary tumors and corresponding tumor-free areas, normal breast tissues from reduction mammoplasty patients, as well as primary mammary gland adenocarcinomas derived from the polyoma virus middle T antigen, or PyMT, mouse model. MCF7 clones expressing individual GFP-tagged SEPT9 isoforms were used to determine their respective intracellular distributions and effects on cell migration. Results An overall increase in gene amplification and altered expression of SEPT9 were observed during breast tumorigenesis. We identified an intragenic alternative promoter at which methylation regulates SEPT9_v3 expression. Transfection of specific GFP-SEPT9 isoforms in MCF7 cells indicates that these isoforms exhibit differential localization and affect migration rates. Additionally, the loss of an uncharacterized SEPT9 nucleolar localization is observed during tumorigenesis. Conclusions In this study, we found conserved in vivo changes of SEPT9 gene amplification and overexpression during human and mouse breast tumorigenesis. We show that DNA methylation is a prominent mechanism responsible for regulating differential SEPT9 isoform expression and that breast tumor samples exhibit distinctive SEPT9 intracellular localization. Together, these findings support the significance of SEPT9 as a promising tool in breast cancer detection and further emphasize the importance of analyzing and targeting SEPT9 isoform-specific expression and function.

2011-01-01

357

Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF7 and MDA-MB-231 human breast cancer cells  

Microsoft Academic Search

Until now, very little has been known about the antioxidant capacity of squalene and its effect on human breast tumourigenesis. In the present work, we investigated squalene’s scavenging properties and its effect on cell proliferation, cell cycle profile, apoptosis, reactive oxygen species (ROS) level and oxidative DNA damage, using human breast cell lines. Our results showed that squalene neither possesses

Fernando Warleta; María Campos; Yosra Allouche; Cristina Sánchez-Quesada; Jesús Ruiz-Mora; Gabriel Beltrán; José J. Gaforio

2010-01-01

358

Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor alpha, epidermal growth factor receptor, c-fos, and c-myc genes.  

PubMed

This study documents a biphasic change in the rate of cell cycle progression and proliferation of T-47D human breast cancer cells treated with synthetic progestins, consisting of an initial transient acceleration in transit through G1, followed by cell cycle arrest and growth inhibition. Both components of the response were mediated via the progesterone receptor. The data are consistent with a model in which the action of progestins is to accelerate cells already progressing through G1, which are then arrested early in G1 after completing a round of replication, as are cells initially in other phases of the cell cycle. Such acceleration implies that progestins act on genes or gene products which are rate limiting for cell cycle progression. Increased production of epidermal growth factor and transforming growth factor alpha, putative autocrine growth factors in breast cancer cells, does not appear to account for the initial response to progestins, since although the mRNA abundance for these growth factors is rapidly induced by progestins, cells treated with epidermal growth factor or transforming growth factor alpha did not enter S phase until 5 to 6 h later than those stimulated by progestin. The proto-oncogenes c-fos and c-myc were rapidly but transiently induced by progestin treatment, paralleling the well-known response of these genes to mitogenic signals in other cell types. The progestin antagonist RU 486 inhibited progestin regulation of both cell cycle progression and c-myc expression, suggesting that this proto-oncogene may participate in growth modulation by progestins. PMID:1922031

Musgrove, E A; Lee, C S; Sutherland, R L

1991-10-01

359

Aberrant Methylation of the Maspin Promoter Is an Early Event in Human Breast Cancer1  

PubMed Central

Abstract The maspin gene functions as a tumor suppressor in human breasts, and its expression is frequently lost during breast cancer progression. In vitro models of human breast cancer indicate that the loss of maspin expression is closely linked to aberrant methylation of the maspin promoter. We conducted a study on 30 archival ductal carcinoma in situ (DCIS) specimens to determine if aberrant methylation of the maspin promoter occurred in vivo, and whether it occurred early in breast cancer evolution. Healthy tissue obtained from reduction mammoplasty was used as normal control. Results from immunohistochemical analysis indicate that maspin expression is lost in a substantial fraction of DCIS specimens (57%). Bisulfite sequencing of DNA isolated from laser capture-microdissected normal and neoplastic ducts showed that loss of maspin expression was often, but not always, linked to aberrant methylation of the maspin promoter, suggesting that other mechanisms, in addition to aberrant methylation, participate and/or cooperate to silence maspin gene expression. Taken together, these results indicate that aberrant methylation of the maspin promoter is an early event in human breast cancer.

Futscher, Bernard W.; O'Meara, Megan M.; Kim, Christina J.; Rennels, Margaret A.; Lu, Di; Gruman, Lynn M.; Seftor, Richard E. B.; Hendrix, Mary J. C.; Domann, Frederick E.

2004-01-01

360

Comparative Impact of Trastuzumab and Cyclophosphamide on HER-2-Positive Human Breast Cancer Xenografts  

PubMed Central

Purpose Metronomic chemotherapy is a minimally toxic and frequently effective new treatment strategy that is beginning to show promising phase II clinical trial results, particularly for metastatic breast cancer when combined with various molecularly targeted antitumor agents. Here, we assessed a treatment strategy that uses trastuzumab plus daily oral metronomic cyclophosphamide on metastatic Her-2–positive human breast cancer models. Experimental Design Treatments were initiated on orthotopic transplanted primary tumors as well as established visceral metastatic disease of two independent Her-2–positive breast cancer models, both independently derived from the human MDA-MB-231 breast cancer cell line. Outcome was assessed by noninvasive measurements of tumor cell–secreted human choriogonadotropin in the urine as a surrogate marker of relative tumor burden, or by whole body bioluminescent imaging, in addition to prolongation of survival. Results Orthotopic primary tumors responded to trastuzumab monotherapy with significant growth delays, whereas minimal antitumor effect was observed when mice with metastatic disease were treated. Nevertheless, trastuzumab showed a benefit in this latter setting when combined with metronomic low-dose cyclophosphamide as assessed by prolongation of survival. This benefit was similar to trastuzumab plus maximum tolerated dose cyclophosphamide, but was associated with lesser toxicity. Conclusions Trastuzumab combined with metronomic cyclophosphamide may be an effective long-term maintenance strategy for the treatment of Her-2–positive metastatic breast cancer.

Francia, Giulio; Man, Shan; Lee, Chyan-Jang; Lee, Christina R.; Xu, Ping; Mossoba, Miriam E.; Emmenegger, Urban; Medin, Jeffrey A.; Kerbel, Robert S.

2009-01-01

361

Detection of high-risk human papillomaviruses in fresh breast cancer samples using the hybrid capture 2 assay.  

PubMed

The etiology of breast cancer remains unknown and the role of human papillomavirus (HPV) in breast carcinogenesis is controversial. This study investigated the prevalence of high-risk HPV infections in Chinese women with breast cancer and the possible relationship between high-risk HPV infection and the clinicopathological characteristics of breast cancer. Tumor cells from 224 fresh breast cancer samples and 37 fresh breast fibroadenomas were collected for hybrid capture 2 (HC2) assay. HC2 was the only technique approved by the United States Food and Drug Administration for screening for high-risk HPV infection in 2008. The prevalence of high-risk HPV infection in breast cancer samples was 21.4%, which was slightly higher than the 16.2% observed in breast fibroadenomas. Age and menopausal status were not risk factors for high-risk HPV infection among breast cancer patients. The clinical and pathological characteristics of breast cancer showed no significant correlation with high-risk HPV infection. Although the prevalence of 13 subtypes of high-risk HPV infections was similar in breast cancer and nonmalignant breast samples, the presence of high-risk HPVs in both malignant and benign breast samples implies that a possible causal role in breast cancer carcinogenesis could not be ruled out. Clarifying the possible link between high-risk HPVs and breast cancer might benefit women vaccinated against HPV and could decrease the incidence of HPV-related breast cancer. J. Med. Virol. 85:2087-2092, 2013. © 2013 Wiley Periodicals, Inc. PMID:23959946

Liang, Weili; Wang, Jianli; Wang, Chongjie; Lv, Yanrong; Gao, Haidong; Zhang, Kai; Liu, Huantao; Feng, Jinbo; Wang, Leiyi; Ma, Rong

2013-08-19

362

Do dogs harbour risk factors for human breast cancer?  

Microsoft Academic Search

Summary We ask consulting patients regularly whether they keep pets in order to identify zoonotic factors. It became apparent that patients with breast carcinoma (N = 69) owned significantly more often dogs but not cats compared to age matched female controls. We compared the frequencies of dog and pet ownership with data from public available statistics on women (N =

B. Laumbacher; B. Fellerhoff; B. Herzberger; R. Wank

2006-01-01

363

Role of Basic Fibroblast Growth Factor in Human Breast Cancer.  

National Technical Information Service (NTIS)

We have demonstrated that recombinant basic fibroblast growth factor (bFGF) inhibits proliferation and promotes programmed cell death in MCF-7 and a number of other breast cancer cells. These effects are opposite of the effects seen in fibroblasts. Since ...

R. Wieder

1997-01-01

364

Prognostic factors for recurrence and survival in human breast cancer  

Microsoft Academic Search

Summary Since only about half of primary breast cancer patients are cured by local treatment, factors which can predict which patients are likely to recur and should thus receive preventive treatmrnt are needed. Here, work on such prognostic factors which has been going on in San Antonio for many years will be reviewed. The significance of the number of involved

Wiliam L. McGuire

1987-01-01

365

Role of Osteopontin in the Malignancy of Human Breast Carcinoma.  

National Technical Information Service (NTIS)

The objective of this research is to establish whether the secreted phosphoprotein osteopontin (OPN) plays a biological role in the progression of breast carcinoma cells, and to determine the nature of this role, by asking if cell properties and genes ass...

F. O'Malley A. B. Tuck

1997-01-01

366

Role of Osteopontin in the Malignancy of Human Breast Carcinoma.  

National Technical Information Service (NTIS)

The objective of this research is to establish whether the secreted phosphoprotein osteopontin (OPN) plays a biological role in the progression of breast carcinoma cells, and to determine the nature of this role, by asking if cell properties and genes ass...

F. O'Malley A. B. Tuck

1999-01-01

367

Role of Osteopontin in the Malignancy of Human Breast Carcinoma.  

National Technical Information Service (NTIS)

The objective of this research is to establish whether the secreted phosphoprotein osteopontin (OPN) plays a biological role in the progression of breast carcinoma cells, and to determine the nature of this role, by asking if cell properties and genes ass...

F. O'Malley A. B. Tuck

1998-01-01

368

Genetic Susceptibility to Cancer Chemotherapy in Human Breast Cancer.  

National Technical Information Service (NTIS)

The treatment of breast cancer patients with chemotherapy is empirical. Even the most active drugs produce meaningful responses in <50% of patients. As a result, too many patients are needlessly exposed to highly toxic drugs and suffer the side effects wi...

W. N. Halt

1999-01-01

369

Genetic Regulation of Lipid Biogenesis in Human Breast Cancer.  

National Technical Information Service (NTIS)

It has been shown that dietary n-6 polyunsaturated fatty acids (PUFAs) promote tumorigenesis and maintain growth of breast cancer cell lines, while n-3 PUFAs generally reduce the incidence and development of cancer and inhibit growth in cell culture. We i...

J. Ntambi

2000-01-01

370

Analyzing the regulation of metabolic pathways in human breast cancer  

Microsoft Academic Search

BACKGROUND: Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer. METHODS: For this, we mapped gene expression data

Gunnar Schramm; Eva-Maria Surmann; Stefan Wiesberg; Marcus Oswald; Gerhard Reinelt; Roland Eils; Rainer König

2010-01-01

371

Transforming Growth Factor-B Receptors in Human Breast Cancer.  

National Technical Information Service (NTIS)

This project addresses the question whether and, if so, how molecular lesions of the genes involved in the TGFB signaling pathway contribute to the origin and/or progression of breast cancer. We have cloned and determined the intron-exon structure of the ...

M. Reiss

1998-01-01

372

CCR5 expression influences the progression of human breast cancer in a p53-dependent manner.  

PubMed

Chemokines are implicated in tumor pathogenesis, although it is unclear whether they affect human cancer progression positively or negatively. We found that activation of the chemokine receptor CCR5 regulates p53 transcriptional activity in breast cancer cells through pertussis toxin-, JAK2-, and p38 mitogen-activated protein kinase-dependent mechanisms. CCR5 blockade significantly enhanced proliferation of xenografts from tumor cells bearing wild-type p53, but did not affect proliferation of tumor xenografts bearing a p53 mutation. In parallel, data obtained in a primary breast cancer clinical series showed that disease-free survival was shorter in individuals bearing the CCR5Delta32 allele than in CCR5 wild-type patients, but only for those whose tumors expressed wild-type p53. These findings suggest that CCR5 activity influences human breast cancer progression in a p53-dependent manner. PMID:14597737

Mañes, Santos; Mira, Emilia; Colomer, Ramón; Montero, Sagrario; Real, Luis M; Gómez-Moutón, Concepción; Jiménez-Baranda, Sonia; Garzón, Alfredo; Lacalle, Rosa Ana; Harshman, Keith; Ruíz, Agustín; Martínez-A, Carlos

2003-11-01

373

CCR5 Expression Influences the Progression of Human Breast Cancer in a p53-dependent Manner  

PubMed Central

Chemokines are implicated in tumor pathogenesis, although it is unclear whether they affect human cancer progression positively or negatively. We found that activation of the chemokine receptor CCR5 regulates p53 transcriptional activity in breast cancer cells through pertussis toxin–, JAK2-, and p38 mitogen–activated protein kinase–dependent mechanisms. CCR5 blockade significantly enhanced proliferation of xenografts from tumor cells bearing wild-type p53, but did not affect proliferation of tumor xenografts bearing a p53 mutation. In parallel, data obtained in a primary breast cancer clinical series showed that disease-free survival was shorter in individuals bearing the CCR5?32 allele than in CCR5 wild-type patients, but only for those whose tumors expressed wild-type p53. These findings suggest that CCR5 activity influences human breast cancer progression in a p53-dependent manner.

Manes, Santos; Mira, Emilia; Colomer, Ramon; Montero, Sagrario; Real, Luis M.; Gomez-Mouton, Concepcion; Jimenez-Baranda, Sonia; Garzon, Alfredo; Lacalle, Rosa Ana; Harshman, Keith; Ruiz, Agustin; Martinez-A., Carlos

2003-01-01

374

Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.  

PubMed

Metastatic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention. PMID:23951338

Fernández-Periáñez, Rodrigo; Molina-Privado, Irene; Rojo, Federico; Guijarro-Muñoz, Irene; Alonso-Camino, Vanesa; Zazo, Sandra; Compte, Marta; Alvarez-Cienfuegos, Ana; Cuesta, Angel M; Sánchez-Martín, David; Alvarez-Méndez, Ana M; Sanz, Laura; Alvarez-Vallina, Luis

2013-08-08

375

Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer.  

PubMed

Immunohistochemical staining of human breast tissues, using an antibody against fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular distribution. Both malignant and non-malignant epithelial cells contained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were negative. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytoplasmic and nuclear elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of FGFR-3, which were present in both malignant and non-malignant epithelial cells. The higher level of nuclear staining and loss of cytoplasmic staining seen in malignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mutations. Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, however, is present in the majority of breast cancers and a different tissue distribution of FGF1 was found in breast tissues, showing predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast cancer. PMID:11329138

Zammit, C; Barnard, R; Gomm, J; Coope, R; Shousha, S; Coombes, C; Johnston, C

2001-05-01

376

Presence of Human Papilloma Virus in a Series of Breast Carcinoma from Argentina  

PubMed Central

Background The etiology and the molecular mechanisms related to breast carcinogenesis remain poorly understood. Some recent reports have examined the role of Human Papillomavirus (HPV) in this disease. The purpose of this study was to determine the prevalence of HPV in breast cancer. Methods Sixty one fresh frozen breast cancers samples were analyzed. Samples were tested for HPV by PCR, and products were automatically sequenced. Findings were correlated with clinical and pathological characteristics. Results The HPV DNA prevalence in the breast cancer samples was 26% (16/61). Clinical parameters were not statistically associated with HPV presence (p>0.05 ?2 test). Sequence analysis in a subgroup of cases indicates the prevalence of low risk HPV11, followed by high risk HPV16. We found no HPV transcriptional activity. Conclusion The present study demonstrated for the first time in Argentina the presence of HPV in a proportion of the malignant breast tissues. This finding suggests that HPV may have a biological significance in breast carcinogenesis.

Pereira Suarez, Ana Laura; Lorenzetti, Mario Alejandro; Gonzalez Lucano, Rene; Cohen, Melina; Gass, Hugo; Vazquez, Paula Martinez; Gonzalez, Pedro; Preciado, Maria V.; Chabay, Paola

2013-01-01

377

Preclinical and Clinical Studies of Gamma Secretase Inhibitors with Docetaxel on Human Breast Tumors  

PubMed Central

Purpose Accumulating evidence supports the existence of breast cancer stem cells (BCSCs), which are characterized by their capacity to self-renew and divide indefinitely, and resistance to conventional therapies. The Notch pathway is important for stem cell renewal, and is a potential target for BCSC-directed therapy. Experimental Design Using human breast tumorgraft studies, we evaluated the impact of gamma secretase inhibitors (GSI) on the BCSC population and the efficacy of combining GSI with docetaxel treatment. The mouse experimental therapy paralleled a concurrent clinical trial in advanced breast cancer patients, designed to determine the maximally tolerated dose of the GSI, MK-0752, administered sequentially with docetaxel, and to evaluate BCSC markers in serial tumor biopsies. Results Treatment with GSI reduced BCSCs in MC1 and BMC-2147 tumorgrafts by inhibition of the Notch pathway. GSI enhanced the efficacy of docetaxel in preclinical studies. In the clinical trial, 30 patients with advanced breast cancer were treated with escalating doses of MK-0752 plus docetaxel. Clinically meaningful doses of both drugs were possible, with manageable toxicity and preliminary evidence of efficacy. A decrease in CD44+/CD24?, ALDH+, and MSFE were observed in tumors of patients undergoing serial biopsies. Conclusions These preclinical data demonstrate that pharmacological inhibition of the Notch pathway can reduce BCSCs in breast tumorgraft models. The clinical trial demonstrates feasibility of combination GSI and chemotherapy, and together these results encourage further study of Notch pathway inhibitors in combination with chemotherapy in breast cancer.

Schott, Anne F.; Landis, Melissa D.; Dontu, Gabriela; Griffith, Kent A.; Layman, Rachel M.; Krop, Ian; Paskett, Lacey A; Wong, Helen; Dobrolecki, Lacey E.; Froehlich, Amber M.; Paranilam, Jaya; Hayes, Daniel F.; Wicha, Max S.; Chang, Jenny C.

2013-01-01

378

Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes*S?  

PubMed Central

Molecular subtypes of breast cancer with relevant biological and clinical features have been defined recently, notably ERBB2-overexpressing, basal-like, and luminal-like subtypes. To investigate the ability of mass spectrometry-based proteomics technologies to analyze the molecular complexity of human breast cancer, we performed a SELDI-TOF MS-based protein profiling of human breast cell lines (BCLs). Triton-soluble proteins from 27 BCLs were incubated with ProteinChip arrays and subjected to SELDI analysis. Unsupervised global hierarchical clustering spontaneously discriminated two groups of BCLs corresponding to “luminal-like” cell lines and to “basal-like” cell lines, respectively. These groups of BCLs were also different in terms of estrogen receptor status as well as expression of epidermal growth factor receptor and other basal markers. Supervised analysis revealed various protein biomarkers with differential expression in basal-like versus luminal-like cell lines. We identified two of them as a carboxyl terminus-truncated form of ubiquitin and S100A9. In a small series of frozen human breast tumors, we confirmed that carboxyl terminus-truncated ubiquitin is observed in primary breast samples, and our results suggest its higher expression in luminal-like tumors. S100A9 up-regulation was found as part of the transcriptionally defined basal-like cluster in DNA microarrays analysis of human tumors. S100A9 association with basal subtypes as well as its poor prognosis value was demonstrated on a series of 547 tumor samples from early breast cancer deposited in a tissue microarray. Our study shows the potential of integrated genomics and proteomics profiling to improve molecular knowledge of complex tumor phenotypes and identify biomarkers with valuable diagnostic or prognostic values.

Goncalves, Anthony; Charafe-Jauffret, Emmanuelle; Bertucci, Francois; Audebert, Stephane; Toiron, Yves; Esterni, Benjamin; Monville, Florence; Tarpin, Carole; Jacquemier, Jocelyne; Houvenaeghel, Gilles; Chabannon, Christian; Extra, Jean-Marc; Viens, Patrice; Borg, Jean-Paul; Birnbaum, Daniel

2008-01-01

379

Biosynthesis of alpha fetoprotein by MCF-7 human breast cancer cells.  

PubMed

Direct evidence was obtained for de novo synthesis of AFP by MCF-7 human breast cancer cells per se. Synthesis was demonstrated by L-14C-leucine and L-35S-methionine incorporation into immunochemically isolated AFP, and confirmed by radioimmunodiffusion and radioimmunoelectrophoresis. This information indicates that AFP synthesis is associated with normal and neoplastic cells of several different histotypes, and suggests that AFP detected and measured previously in primary human breast cancer tissue cytosol (Sarcione et al., 1983) also resulted from in situ biosynthesis by breast cancer cells per se rather than uptake of exogenous AFP originating from extracellular sources. Evidence that AFP obtained after treatment of 14C-leucine radiolabelled MCF-7 breast cancer cell protein with 0.4 M KCl contained 2.6 times more radioactivity than did AFP obtained before such salt treatment is interpreted as indicating that two different molecular species of de novo synthesized AFP existed in breast cancer cells: (1) larger amount of non-immunoreactive AFP which became immunoreactive and measurable after KCl treatment, and (2) smaller amounts of free immunoreactive AFP. 14C-radiolabelled AFP obtained before and after treatment of cell protein with 0.4 M KCl codiffused, comigrated with alpha 1 electrophoretic mobility and gave an identical radioimmunologic reaction both with each other and with added carrier human cord serum AFP. Furthermore, preliminary studies indicated that radiolabelled non-immunoreactive AFP could be separated from lower-molecular-weight free AFP by chromatography on Sephadex G-200. Taken together, these findings suggest that synthesized free AFP was bound as a non-immunoreactive high-molecular-weight macromolecular complex rather than being covalently linked. Our current working hypothesis is that most of the de novo synthesized endogenous AFP in MCF-7 human breast cancer cells was rapidly and reversibly bound by hydrophobic bonding to a specific cytoplasmic AFP-receptor. PMID:2579036

Sarcione, E J; Hart, D

1985-03-15

380

Effects of Ambient Particulate Matter on Human Breast Cancer: Is Xenogenesis Responsible?  

PubMed Central

Background Recently, evidence from several studies has revealed that air pollution is associated with the increased morbidity and mortality of breast cancer patients. However, to date, the underlying mechanism remains largely unclear. Considering the high prevalence of air pollution and breast cancer in China, it is necessary to understand how air pollution may affect breast cancer. Methods We analyzed 1,832 female patients who had resided in the same cities for at least 10 years prior to their diagnosis. Variables including demographic data as well as clinical and tumor characteristics, including the patient’s age at menarche, family history of breast cancer, tumor histopathological type, tumor size, lymph node metastasis, distant metastasis, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER-2) status at the time of diagnosis were analyzed. Results Compared to patients residing in low-pollution areas, patients living in high-pollution areas demonstrated a younger age at menarche (p<0.001), a greater family history of breast cancer (p?=?0.034) and more invasive cancers (p?=?0.028) with higher tumor grades (p?=?0.028) and estrogen receptor (ER)-positive status (p?=?0.022). Differences in tumor grade were only found in ER-positive cases. Conclusions Our findings and clinical data indicate that long-term air pollution exposure may contribute to the development of breast cancer by playing the role of a xenoestrogen, and also provides new insight into the association between air pollution and the morbidity and mortality of breast cancer patients. Furthermore, it is urgently necessary to study the association between air pollution and breast cancer to improve the living quality and health of females, and applicable public health strategies may need to be established or modified as soon as possible.

Huo, Qiang; Zhang, Ning; Wang, Xiaolong; Jiang, Liyu; Ma, Tingting; Yang, Qifeng

2013-01-01

381

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer  

PubMed Central

Background The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. Materials and Methods All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). Results EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk – EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. Conclusions We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

Glenn, Wendy K.; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J.; Lawson, James S.

2012-01-01

382

Hypoxic Conditions Induce a Cancer-Like Phenotype in Human Breast Epithelial Cells  

PubMed Central

Introduction Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis. Methods Normal human primary breast epithelial cells and immortalized non-malignant mammary epithelial MCF-10A cells were grown in a three-dimensional overlay culture on laminin-rich extracellular matrix for up to 21 days at normoxic or hypoxic conditions. Acinar morphogenesis and expression of markers of epithelial differentiation and cell polarization were analyzed by immunofluorescence, immunohistochemistry, qPCR and immunoblot. Results In large ductal carcinoma in situ patient-specimens, we find that epithelial cells with high HIF-1? levels and multiple cell layers away from the vasculature are immature compared to well-oxygenated cells. We show that hypoxic conditions impaired acinar morphogenesis of primary and immortalized breast epithelial cells grown ex vivo on laminin-rich matrix. Normoxic cultures formed polarized acini-like spheres with the anticipated distribution of marker proteins associated with mammary epithelial polarization e.g. ?6-integrin, laminin 5 and Human Milk Fat Globule/MUC1. At hypoxia, cells were not polarized and the sub-cellular distribution pattern of the marker proteins rather resembled that reported in vivo in breast cancer. The hypoxic cells remained in a mitotic state, whereas proliferation ceased with acinar morphogenesis at normoxia. We found induced expression of the differentiation repressor ID1 in the undifferentiated hypoxic MCF-10A cell structures. Acinar morphogenesis was associated with global histone deacetylation whereas the hypoxic breast epithelial cells showed sustained global histone acetylation, which is generally associated with active transcription and an undifferentiated proliferative state.

Vaapil, Marica; Helczynska, Karolina; Villadsen, Rene; Petersen, Ole W.; Johansson, Elisabet; Beckman, Siv; Larsson, Christer; Pahlman, Sven; Jogi, Annika

2012-01-01

383

Organochlorine residues in human breast milk: analysis through a sentinel practice network  

Microsoft Academic Search

STUDY OBJECTIVE--The study aimed to assess through a sentinel practice network the validity of data on levels of organochlorine residues in human milk along with personal, lifestyle, and exposure variables of breastfeeding women; to compare the results of this new approach with those of the Lower Saxony breast milk surveillance programme; and to test hypotheses on potential determinants of contamination

M Schlaud; A Seidler; A Salje; W Behrendt; F W Schwartz; M Ende; A Knoll; C Grugel

1995-01-01

384

beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts  

Microsoft Academic Search

1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of 1 integrin signaling. We showed previously that 1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix

Catherine C. Park; Hui J. Zhang; Evelyn S. Yao; Chong J. Park; Mina J. Bissell

2008-01-01

385

Natural history of human breast cancer: Recent data and clinical implications  

Microsoft Academic Search

Summary This study of the natural history of human breast cancer was based on the analysis of a series of 3000 patients treated by radical mastectomy at a single institution (Institut Gustave Roussy) at a time when adjuvant chemotherapy was not prescribed. The follow-up of the patients ranged from 15 to 30 years; for each patient the tumor size, the

Maurice Tubiana; Serge Koscielny

1991-01-01

386

Antiproliferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line  

Microsoft Academic Search

Ethanolic extracts of selected nine Thai medicinal plants were tested for antiproliferative activity against SKBR3 human breast adenocarcinoma cell line using MTT assay. Garcinia mangostana showed the most potent activity. However, all plant extracts showed activity in potential range for further investigation on cancer cells.

Primchanien Moongkarndi; Nuttavut Kosem; Omboon Luanratana; Suna Jongsomboonkusol; Narongchai Pongpan

2004-01-01

387

Antiproliferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line  

Microsoft Academic Search

Ethanolic extracts of selected nine Thai medicinal plants were tested for antiproliferative activity against SKBR3 human breast adenocarcinoma cell line using MTT assay. Garcinia mangostana showed the most potent activity. However, all plant extracts showed activity in potential range for further investigation on cancer cells. 2004 Elsevier B.V. All rights reserved.

Primchanien Moongkarndi; Nuttavut Kosem; Omboon Luanratana; Suna Jongsomboonkusol; Narongchai Pongpanb

2004-01-01

388

Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties  

Microsoft Academic Search

The epithelial compartment of the human breast comprises two distinct lineages: the luminal epithelial and the myoepithelial lineage. We have shown previously that a subset of the luminal epithelial cells could convert to myoepithelial cells in culture signifying the possible existence of a progenitor cell. We therefore set out to identify and isolate the putative precursor in the luminal epithelial

Thorarinn Gudjonsson; Helga Lind Nielsen; Lone Rønnov-Jessen; Mina J. Bissell; Ole William Petersen

2002-01-01

389

Assessing a Drosophila Metastasis Model in Mouse and Human Breast Cancer.  

National Technical Information Service (NTIS)

We propose to combine our expertise to target a process that is critical to breast cancer metastasis that is likely conserved in flies, mice and humans. The advantages of addressing the question of metastasis through the combined expertise of the Cagan an...

K. Weilbaecher R. Cagan

2008-01-01

390

P1, a high mobility group-like protein is depressed in human breast adenocarcinoma  

Microsoft Academic Search

Protein P1, which is a nuclear protein resembling high mobility group proteins, has been studied in human breast adenocarcinomas and compared to those from control tissue. The presence of the protein was confirmed by in vitro phosphorylation by casein kinase II and immunoblotting, using antibodies raised in rabbits against rat liver P1. The protein has been isolated by reverse phase

Anna Photopoulou; Theocharis Patargias; Vassiliki Aleporou-Marinou

2001-01-01

391

An In Vitro Model That Recapitulates the Epithelial to Mesenchymal Transition (EMT) in Human Breast Cancer  

Microsoft Academic Search

The epithelial to mesenchymal transition (EMT) is a developmental program in which epithelial cells down-regulate their cell-cell junctions, acquire spindle cell morphology and exhibit cellular motility. In human breast cancer, invasion into surrounding tissue is the first step in metastatic progression. Here, we devised an in vitro model using selected cell lines, which recapitulates many features of EMT as observed

Elad Katz; Sylvie Dubois-Marshall; Andrew H. Sims; Philippe Gautier; Helen Caldwell; Richard R. Meehan; David J. Harrison; Syed Aziz

2011-01-01

392

Prognostic Significance of the Metastasis-associated Protein Osteopontin in Human Breast Cancer1  

Microsoft Academic Search

The adhesive glycophosphoprotein (OPN) is capable of inducing me- tastasis in rodent models of breast cancer. We now show that a mono- clonal antibody to rat OPN recognizes specifically human OPN using Western blotting techniques and used it to assess the prognostic signifi- cance of OPN in primary tumors of a group of 333 patients treated between 1976 and 1982

Philip S. Rudland; Angela Platt-Higgins; Mohamed El-Tanani; Roger Barraclough; John H. R. Winstanley; Rachel Howitt; Christopher R. West

2002-01-01

393

Role of Terbium and Gadolinium in Reversal of Cisplatin Resistance in Cultured Human Breast Cancer Cells.  

National Technical Information Service (NTIS)

This proposal was an innovative endeavor to unravel the intracellular signaling events that occur when terbium ions (Tb3+) or gadolinium ions (Gd3+) are added to cisplatin treatment of cisplatin resistant MDA-MB231 human breast cancer cells Preliminary da...

A. E. Allworth

2001-01-01

394

The effect of age and menstrual cycle upon proliferative activity of the normal human breast  

Microsoft Academic Search

The aim of this study was to determine the proliferative activity within the epithelial cells of the normal human breast in 122 patients (6 reduction mammoplasties and 116 fibroadenoma excisions) in relation to age and the phase of the menstrual cycle. Thirty three of the patients were on oral contraceptives and 33 were parous. Thin tissue slices were incubated with

CS Potten; RJ Watson; GT Williams; S Tickle; SA Roberts; M Harris; A Howell

1988-01-01

395

Glycosphingolipid composition of MDA-MB-231 and MCF7 human breast cancer cell lines  

Microsoft Academic Search

Much evidence has shown that glycosphingolipids are involved in cellular recognition, regulation of cell growth, and metastasis. In the present study, the major glycosphingolipids of two widely studied human breast cancer cell lines were examined. The MCF-7 cell line has functional estrogen and EGF receptors, is dependent on estrogen and EGF for growth, and is uninvasive, while MDA-MB-231 cells are

Keiko Nohara; Fang Wang; Sarah Spiegel

1998-01-01

396

Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells1  

Microsoft Academic Search

Cancer cells invade by secreting degradative enzymes, which are sequestered in lysosomal vesicles. In this study, the impact of an acidic extracellular environ- ment on lysosome size, number, and distance from the nucleus in human mammary epithelial cells (HMECs) and breast cancer cells of different degrees of malignancy was characterized because the physiolog- ical microenvironment of tumors is frequently charac-

Kristine Glunde; Sandra E. Guggino; Meiyappan Solaiyappan; Arvind P. Pathak; Yoshitaka Ichikawa; Zaver M. Bhujwalla

397

Development of Ligand-Transformed Alpha-Fetoprotein for Use Against Breast Cancer in Humans.  

National Technical Information Service (NTIS)

The purpose of this study was to produce large quantities of the active form of alpha-fetoprotein (AFP) and assess its effectiveness in the control of estrogen-stimulated growth of experimental human breast cancers. Both recombinant and natural AFP were p...

J. A. Bennett

1999-01-01

398

Identification of Cellular Binding Sites for a Novel Human Anti-Breast Cancer Peptide.  

National Technical Information Service (NTIS)

We have synthesized a nine amino acid peptide, AFPep, that inhibits the growth of ER+ human breast. Understanding the process by which AFPep mediates its inhibitory activity is extremely important for the development of this drug or other drugs which expl...

L. DeFreest J. Bennett

2004-01-01

399

Association Between Nitrotyrosine Levels and Microvascular Density in Human Breast Cancer  

Microsoft Academic Search

Nitrotyrosine (NO2Y) is a global marker of protein modification by reactive nitrogen species such as peroxynitrite derived from nitric oxide (NO). Because NO and its derivatives are postulated to enhance carcinogenesis, we used stable isotope dilution mass spectrometry to measure the levels of NO2Y in 30 samples of human breast cancer of varying pathologic types. In the samples tested, the

Michael Samoszuk; Marie-Luise Brennan; Vu To; Leonard Leonor; Lemin Zheng; Xiaoming Fu; Stanley L. Hazen

2002-01-01

400

Identification of arsenic-binding proteins in human breast cancer cells  

Microsoft Academic Search

As a cancer chemotherapeutic drug, arsenic acts on numerous intracellular signal transduction pathways in cancer cells. However, its mechanism of actions is still not fully understood. Previous studies suggest that arsenic reacts with closely spaced cysteine (Cys) residues of proteins with high Cys content and accessible sulfhydryl (SH) groups. In this study, human breast cancer cell line MCF-7 was examined

Xinyan Zhang; Fan Yang; Joong-Youn Shim; Kenneth L. Kirk; D. Eric Anderson; Xiaoxin Chen

2007-01-01

401

Induction of apoptosis in human breast cancer cells by a pulsed atmospheric pressure plasma jet  

Microsoft Academic Search

By using an atmospheric pressure plasma jet driven by pulsed dc voltage with repetition rate of several tens of kilohertz, we were able to induce apoptosis in cultured human breast cancer cells (MCF-7). The apoptotic changes in cells with plasma treatment were detected by flow cytometry and fluorescence staining assay. A significant portion of these cells was observed to exhibit

Sun Ja Kim; T. H. Chung; S. H. Bae; S. H. Leem

2010-01-01

402

Role of Integrins and IGFBPs in the IGF-1 Stimulated Migration of Human Breast Cancer Cells.  

National Technical Information Service (NTIS)

We have previously shown that IGF-I stimulates chemotaxis of MCF-7 and MDA-23 1 human breast cancer cells. We now report that PDGF is a potent stimulant of migration. FGF is less effective, and EGF has no effects. The integrins that are present on 4 addit...

B. Zheng D. D. Clemmons

1999-01-01

403

Subcellular Localization and Distribution of the Breast Cancer Resistance Protein Transporter in Normal Human Tissues1  

Microsoft Academic Search

High expression of the Breast Cancer Resistance Protein (BCRP) gene has been shown to be involved in resistance to chemotherapeutic drugs. Knowledge of the localization of BCRP protein in normal tissues may help unravel the normal function of this protein. Therefore, we characterized the tissue distribution and cellular localization of BCRP in frozen sections of normal human tissues. For this

Marc Maliepaard; George L. Scheffer; Ian F. Faneyte; Margot A. van Gastelen; Adriana C. L. M. Pijnenborg; Alfred H. Schinkel; Marc J. van de Vijver; Rik J. Scheper; Jan H. M. Schellens

2001-01-01

404

Suberoylanilide Hydroxamic Acid as a Potential Therapeutic Agent for Human Breast Cancer Treatment  

Microsoft Academic Search

Background: Suberoylanilide hydroxamic acid (SAHA) is a prototype of the newly developed, second-generation, hybrid polar compounds. It is a novel histone deacetylase inhibitor with high potency for inducing cell differentiation of cultured murine erythroleukemia cells. Studies with SAHA have primarily been performed with hematopoietic tumor cells. Here we extent these studies with SAHA to human breast cancer cell lines in

Lili Huang; Arthur B. Pardee

2000-01-01

405

Reversal of Doxorubicin Resistance in Human Breast Adenocarcinoma (MCF- 7) Cells by Liposomal Monensin.  

National Technical Information Service (NTIS)

The purpose of the present study was to overcome the doxorubicin resistance in human breast adenomacarcinom (MCF-7/dox) cells by the delivery of monensin in long-circulating (stealth) liposomes (SML). We have previously shown that SML could enhance the cy...

M. S. Sachdeva K. Agrawal

2002-01-01

406

In Vivo Gene Expression Profile Analysis of Human Breast Cancer Progression1  

Microsoft Academic Search

The development and use of molecular-based therapy for breast cancer and other human malignancies will require a detailed molecular genetic analysis of patient tissues. Th