DANIEL M MEDINA

..Thus, many different models will be needed to fully enable an understanding of the cellular and molecular basis for human breast cancer and eventually provide the critical preventive and therapeutic approaches to conquer this cancer...

..Therefore, we asked whether SAFB1 heterozygosity would influence tumor development and progression in MMTV-Wnt-1 oncomice or DMBA induced tumorigenicity, in a manner consistent with haploinsufficiency of the remaining allele...

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..The experiments reported here address the question of whether a short-term hormone treatment can prevent mammary tumorigenesis in two different genetically engineered mouse models...

..To set the stage for functional experiments on this molecule, we examined the developmental expression and localization of claudin 7 in the murine mammary epithelium and in a selection of murine mammary tumors...

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..The results demonstrate that the chemical-carcinogen treated stroma did not enhance mammary tumorigenesis in this model and that carcinogen treatment of the mammary epithelium was essential for tumorigenesis...

..These results show that tamoxifen delays the emergence of ER-alpha-negative tumors if given early in premalignant progression...

..The current studies have moved this research area from the biological to the molecular realm and offer the potential for directing prevention efforts at specific molecular targets...

..Newer transgenic mouse models provide a renewed opportunity to engage in the study of the mechanisms and processes underlying mammary metastasis...

..Analogous hyperplasias from several defined genetic models, adequately characterized at the biological and molecular levels, would provide appropriate models for testing chemopreventive agents...

..These results demonstrate that p53 plays a pivotal role in hormone-induced protection and raises the question of the mechanisms by which the steroid hormones, estrogen and progesterone, functionally activate p53...

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..Our results indicate that a short prior exposure to chloroquine may have a preventative application for mammary carcinogenesis...

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..Several possible explanations of the puzzling relationship between elimination of cycling cells and increased tumor incidence are discussed and alternative strategies for the prevention of breast cancer are proposed...

..Collectively, the effects of cyclin D2 overexpression on mammary gland development during pregnancy and involution are attributed to two major factors, altered p27(kip1) protein level and inhibition of cyclin D1 phosphorylation...

..These results collectively suggest that Separase is an oncogene, whose overexpression alone in mammary epithelial cells is sufficient to induce aneuploidy and tumorigenesis in a p53 mutant background...

..These results demonstrate that, on a background of underlying genetic instability, very low doses of environmental mutagens and mitogens can produce strong cocarcinogenic effects...

..This model would appear an excellent one to test the effects of chemopreventive agents on the development of both ER-negative and ER-positive mammary tumors...

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..Additionally, the experiments highlight the usefulness of transgenic mouse models in the testing of hypotheses derived from the classic rat mammary models...

..Collectively, these data suggest that the carcinogen MNU induces changes resulting in genetic instability detectable before hyperplasia and tumors develop in the rat mammary gland...

..Cumulatively, these results suggest that ratAurA overexpression and centrosome amplification were linked to tumor development and progression and may serve as early markers in tumorigenesis...

..This review provides an overview of gene alterations in the cell cycle components in mouse mammary hyperplasia...

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..This is the first study to examine the transcriptome of very early stages of preneoplastic progression in an in vivo model that mimics human breast cancer...

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..Furthermore, this p53-null mouse mammary tumor model may allow us to identify new CSC markers and to test the functional importance of these markers...

..The second modifier mapped is Mtsm2, a recessive-acting modifier. Mtsm2 is located on chromosome X and is significantly linked to mammary tumorigenesis (p = 1.03 x 10(-7))...

..Our results suggest that AIB1 may serve as a potential target for prevention of carcinogen-induced breast cancer initiation and for treatment of breast cancer progression...

..One central question that is still unresolved is whether the refractoriness is intrinsic to the mammary epithelial cells and/or mediated by persistent alterations in the host environment...

..These data indicate that appropriate levels of p53 activity are important in regulating mammary gland ductal morphogenesis, in part through regulation of the IGF-1 pathway...

..Further functional studies of metastasis signature genes should help to develop means to curb the metastasis process...

..In summary, this model allows one to analyze the biological, genetic and molecular consequences of p53 gene deletion in the in situ mammary gland by taking advantage of transplantation methods. ..

..These experiments will increase the understanding of regulation of the growth and tumorigenic progression of mammary preneoplasias and provide a model system for understanding regulation of growth in early stage breast cancer. ..

..The hypothesis that the chemopreventive effects of selenium on cell growth are mediated by modification of protein function will be pursued by examining protein phosphorylation and protein synthesis...

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..The molecular understanding of the fundamental biological events involved in hormone-induced growth and differentiation will provide a rationale for developing new approaches for preventing human breast cancer. ..