... Accession Number : ADA541877. Title : Induction and Acceleration of Mammary Tumors by Activated P13 Kinase. Descriptive ...
DTIC Science & Technology
The transforming growth factor-betas (TGF{beta}s) are members of a large superfamily of pleiotropic cytokines that also includes the activins and the bone morphogenetic proteins (BMPs). Members of the TGF{beta} family regulate complex physiological processes such cell proliferation, differentiation, adhesion, cell-cell and cell-matrix interactions, motility, and cell death, among others (Massague, ...
DOE Information Bridge
Mammary myoepithelial cells have been the foster child of breast cancer biology and have been largely ignored since they were considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge in stem cell biology and the cellular microenvironment has been increasing ...
Energy Citations Database
... mammary neoplasia. Moreover, mammary glands from MMTV-DLC1- Ser88Ala mice had accelerated involution. Together ...
Wnt-1 transgenic(TG) mice develop mammary tumors at a high rate by 1 year of age due to mammary gland overexpression of the Wnt-1 oncogene. - We have shown that p53-deficiency accelerates mammary tumorigenesis in these mice, with 100% of p53-1- Wnt-1 TG m...
National Technical Information Service (NTIS)
... Mammary tumorigenesis is further accelerated in p53-deficient Wnt-1 TG mice generated by mating Wnt-1 TG mice with p53-knockout mice. ...
The ectopic expression of the Wnt-1 proto-oncogene in Wnt-1 transgenic (Wnt-1 TG) mice results in mammary gland hyperplasia and early adenocarcinoma development. Mammary tumorigenesis is further accelerated in p53-deficient Wnt-1 TG mice generated by mati...
4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80mg/kg or 160mg/kg) and monitored for 22 months for ...
PubMed
RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK. Mammary glands of RANK- and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of ...
To characterize the role of BRCA1 in mammary gland development and tumor suppression, a transgenic mouse model of BRCA1 overexpression was developed. Using the mouse mammary tumor virus (MMTV) promoter/enhancer, transgenic mice expressing human BRCA1 or select mutant controls were generated. Transgenic animals examined during adolescence were shown to ...
PubMed Central
Estrogen receptor (ER) is a key regulator of mammary gland development and is also implicated in breast tumorigenesis. Because ER-mediated activities depend critically on coregulator partner proteins, we have investigated the consequences of reduction or loss of function of the coregulator repressor of ER activity (REA) by conditionally deleting one allele or both alleles of ...
Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only ...
NASA Astrophysics Data System (ADS)
We show that the metalloproteinase matrilysin dramatically accelerates the development of neu-induced mammary tumors by decreasing the time to tumor onset and increasing the percent of animals developing tumors. In addition, MMTV-matrilysin transgenic mic...
Current utilization of the linear accelerator as well as 5-year cumulative experience in radiotherapy is presented. Cutaneous lymphomas and mammary gland carcinomas were the prime experience region; however, cancers at other locations were treated with mi...
Serum growth hormone (GH) was suppressed in female rats bearing mammary tumors induced by 7, 12, dimethylbenz(a)anthracene (DMBA) or N-nitrosomethylurea(NMU). Serum GH was suppressed due to treatment with a human GH analog produced by the plerocercoid stage of the tapeworm Spirometra mansonoides. Rats treated with plerocercoid growth factor (PGF) via plerocercoid infection had ...
Novel therapeutic agents combined with innovative modes of delivery and non-invasive imaging of drug delivery, pharmacokinetics and efficacy are crucial in developing effective clinical anticancer therapies. In this study, we have created and characterized multiple novel variants of anti-angiogenic protein thrombospondin (aaTSP-1) that comprises unique regions of three type-I-repeats of TSP-1 and ...
Epidemiological studies indicate that parity enhances HER2/ErbB2/Neu-induced breast tumorigenesis. Furthermore, recent studies using multiparous, ErbB2/Neu-overexpressing mouse mammary tumor virus (MMTV-Neu) mice have shown that parity induces a population of cells that are targeted for ErbB2/Neu-induced transformation. Although parity accelerates ...
The cytokine-transforming growth factor beta1 (TGFB1) is implicated in development of the mammary gland through regulation of epithelial cell proliferation and differentiation during puberty and pregnancy. We compared mammary gland morphogenesis in virgin Tgfb1(+/+), Tgfb1(+/-), and Tgfb1(-/-) mice and transplanted Tgfb1(+/+) and Tgfb1(-/-) epithelium to ...
Cdc25 A and B are dual-specificity phosphatases which have been implicated in neoplastic transformation. Although Cdc25A and Cdc25B have been found to be over-expressed in many cancer cell lines and primary tumors, the physiological roles of Cdc25A and B in vivo are largely undefined. To investigate the roles of these proteins in the oncogenic transformation of the mammary ...
This study examined the development of N-methyl-N-nitrosourea (MNU)-induced mammary carcinomas in young and old female Lewis rats following short-term treatment with estrogen and progesterone to mimic pregnancy. Rats exposed at 4 weeks of age to MNU were treated at 6 weeks of age (early MNU/young E/P treatment) or at 24 weeks of age (early MNU/old E/P treatment) with a 21-day ...
IntroductionBreast cancer is genetically and clinically a heterogeneous disease. However, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. Recently, we discovered an interaction between Wnt and integrin-linked kinase (ILK) within the signaling cascade that regulates cell growth and survival. Interestingly, ...
We have observed that lactating mouse dams nursed 4 times per day (4X) maintained lactation, but had lower milk yields by the weigh-suckle-weigh method, than dams nursed ad libitum (AL). Therefore, we hypothesized that decreased nursing frequency would also decrease lactation persistence, increase m...
Technology Transfer Automated Retrieval System (TEKTRAN)
WAPT121 transgenic mice express T121, a trucation mutation of SV40 antigen that binds and inactivates all pRB-related proteins, under control of whey acidic protein (WAP) promoter. T121 expression was detected in the mammary gland (Simin et al., 2004). Transgenic females failed to nurse pups because of lactation defects. Multi-pregnant females developed ...
Cancer.gov
Spy1A is a unique cell cycle activator known to mediate cell cycle progression and override the DNA damage response. This study focused on determining the role of this protein on postnatal mammary gland morphogenesis and neoplasia. Herein, we show that Spy1A levels are tightly regulated during mammary gland development and that ectopic expression ...
Overexpression and/or amplification of the ErbB-2 oncogene as well as inactivation of the PTEN tumor suppressor are two important genetic events in human breast carcinogenesis. To address the biological impact of conditional inactivation of PTEN on ErbB-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the murine ...
Signalling through the janus kinase (JAK)/signal transducer and activator of transcription (Stat) pathway is required at different stages of mammary gland development, and this pathway is frequently hyper-activated in cancer, including tumours of the breast. Stats 3, 5 and 6 have important roles in the differentiation and survival of mammary alveolar ...
The proapoptotic proteinase inhibitor TIMP-3 is the only molecule of this family thought to influence cell death. We examined epithelial apoptosis in TIMP-3�deficient mice during mammary gland involution. Lactation was not affected by the absence of TIMP-3, but glandular function, as measured by gland-to-body weight ratio and production of ?-casein, was suppressed earlier ...
The proapoptotic proteinase inhibitor TIMP-3 is the only molecule of this family thought to influence cell death. We examined epithelial apoptosis in TIMP-3-deficient mice during mammary gland involution. Lactation was not affected by the absence of TIMP-3, but glandular function, as measured by gland-to-body weight ratio and production of beta-casein, was suppressed earlier ...
Cow's milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague-Dawley rats were given either whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and ...
Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds. Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one ...
Tissue microenvironment is an important determinant of carcinogenesis. We demonstrate that ionizing radiation, a known carcinogen, affects cancer frequency and characteristics by acting on the microenvironment. Using a mammary chimera model in which an irradiated host is transplanted with oncogenic Trp53 null epithelium, we show accelerated development of ...
BackgroundMMTV-Wnt1 transgenic mice develop mammary hyperplasia early in development, followed by the appearance of solitary mammary tumors with a high proportion of cells expressing early lineage markers and many myoepithelial cells. The occurrence of tumors is accelerated in experiments that activate FGF proto-oncogenes or remove the ...
ObjectiveCombined hormone replacement therapy (HRT) containing estrogen and progestin (medroxyprogesterone acetate [MPA]) leads to increased risk of breast cancer in postmenopausal women, compared with HRT regimens containing estrogen alone, or placebo. We previously reported that, in animal models, progestins can accelerate the development of mammary ...
SnoN is an important negative regulator of transforming growth factor-? (TGF-?) signaling that was originally identified as a transforming oncogene in chicken embryonic fibroblasts. Both pro-oncogenic and antioncogenic activities of SnoN have been reported, but its function in normal epithelial cells has not been defined. In the mouse mammary gland, SnoN is expressed at ...
Genetically defined mouse models offer an important tool to identify critical secondary genetic alterations with relevance to human cancer pathogenesis. We used newly generated MMTV-Cre105Ayn mice to inactivate p53 and/or Rb strictly in the mammary epithelium and to determine recurrent genomic changes associated with deficiencies of these genes. p53 inactivation led to ...
Breast cancer cell lines that express the nuclear peroxisome proliferator-activated receptor ? (PPAR?) can be prompted to undergo growth arrest and differentiation when treated with synthetic PPAR? ligands. To evaluate the therapeutic potential of increased PPAR? signaling in vivo, we generated transgenic mice that express a constitutively active form of PPAR? in mammary ...
Breast cancer cell lines that express the nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) can be prompted to undergo growth arrest and differentiation when treated with synthetic PPAR gamma ligands. To evaluate the therapeutic potential of increased PPAR gamma signaling in vivo, we generated transgenic mice that express a constitutively active form of PPAR gamma in ...
In order to assess the effect of early prolactin suppression on the subsequent development of dimethylbenz(a)anthracene (DMBA)-induced mammary cancers, the dopamine agonist, CB-154, was chronically administered to female Sprague-Dawley rats from Day 35 to Day 50 of age. DMBA was then administered and tumor development assessed over a 25-week period. It was found that animals ...
Current utilization of the linear accelerator as well as 5-year cumulative experience in radiotherapy is presented. Cutaneous lymphomas and mammary gland carcinomas were the prime experience region; however, cancers at other locations were treated with mixed-beam therapy; employing fast neutrons and photon beams. The technique appears promising for ...
Estrogens have important functions in mammary gland development and carcinogenesis. To better define these roles, we have used two previously characterized lines of genetically altered mice: estrogen receptor-alpha (ER alpha) knockout (ERKO) mice, which lack the gene encoding ER alpha, and mouse mammary virus tumor (MMTV)-Wnt-1 transgenic mice (Wnt-1 TG), ...
The stress-activated protein kinase (SAPK) p38 can induce apoptosis, and its inhibition facilitates mammary tumorigenesis. We found that during mammary acinar morphogenesis in MCF-10A cells grown in three-dimensional culture, detachment of luminal cells from the basement membrane stimulated mitogen-activated protein kinase (MAPK) kinases 3 and 6 (MKK3/6) ...
The use of progestins as a component of hormone replacement therapy has been linked to an increase in breast cancer risk in postmenopausal women. We have previously shown that medroxyprogesterone acetate (MPA), a commonly administered synthetic progestin, increases production of the potent angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells, leading to the development of new ...
... in these studies is that overexpression of USF in the mammary glands of transgenic ... form or USF-2 was targeted to the mammary gland under the ...
... salivary and mammary glands. ... mechanisms responsible for the initiation of branching, especially in the mammary gland, remain to be determined. ...
... effects of myoepithelial cells on mammary development because the K5 promoter directs transgene expression in mammary glands exclusively to ...
... role in mammary gland development and tumorigenesis. Descriptors : *ORGANS(ANATOMY), *MAMMARY GLANDS, *ONCOGENIC VIRUSES ...
... receptor for the avian virus Rous sarcoma virus in mammary ... MAMMARY GLANDS, RETROVIRUSES, ONCOGENIC VIRUSES, SARCOMA VIRUS. ...
... whether int-3 is expressed in the mammary gland and whether this expression is developmentally regulated. ... neoplastic mammary glands. ...
... Abstract : The Whn transcription factor plays an essential role in the development and maturation of mammary glands, as mammary glands in the ...
... to determine if the expression of the kinases is regulated during mammary gland development, RNA was isolated from mammary glands of FVB ...
... In Utero Exposure to Cadmium, Mammary Gland Development, and Breast Cancer Risk ... the effects of estrogens in the mammary glands and uterus ...
... TITLE: Hormonal Regulation of Mammary Gland Development and Breast Cancer ... extended for lactating mammary gland tissue. ...
... and that haploinsufficiency of CBP does not appear to affect mammary gland development. Descriptors : *MAMMARY GLANDS, *BREAST CANCER ...
... modulate the development, function, and involution of the mammary gland epithelium. Difficulty in studying the mammary gland is also ... ...
NBII National Biological Information Infrastructure
... these cells in primary mammary epithelial cell cultures. ... and lobulogenesis (ie these cells have important features of mammary stem cells). ...
... Cancer Prevention by Hormonally Induced Mammary Gland Differentiation: The Role of a Novel Mammary Growth Inhibitor and Differentiation ...
The tumor suppressor gene p53 has an apparent role in breast tumor development in humans, as approximately 30% of sporadic tumors acquire p53 mutations and Li-Fraumeni syndrome patients carrying germ line p53 mutations frequently develop breast tumors at early age. In the present study, conditional expression of a targeted mutation is used to analyze the role of the human R273H tumor-associated ...
BRCA1 can regulate estrogen receptor-? (ER?) activity. This study tested the hypotheses that Brca1 loss in mammary epithelium alters the estrogenic growth response and that exposure to increased estrogen or ER? collaborates with Brca1 deficiency to accelerate preneoplasia and cancer development. Longer ductal extension was found in ...
... in Prlr(+/-) mammary glands but increased in Elf5(+/-) mammary glands. ... proliferation to differentiation within the mammary gland during pregnancy. ...
