PMID:11535819

Citation	Stanbrough, M, Leav, I, Kwan, PW, Bubley, GJ and Balk, SP (2001) Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium. Proc. Natl. Acad. Sci. U.S.A. 98:10823-8
Abstract	Prostate cancer (PCa) is an androgen dependent disease that can be treated by androgen ablation therapy, and clinical trials are under way to prevent PCa through the reduction of androgen receptor (AR) activity. However, there are no animal models of AR-mediated prostatic neoplasia, and it remains unclear whether the AR is a positive or negative regulator of cell growth in normal prostate secretory epithelium. To assess the direct effects of the AR in prostate epithelium, a murine AR transgene regulated by the rat probasin promoter (Pb) was used to generate transgenic mice expressing increased levels of AR protein in prostate secretory epithelium. The prostates in younger (<1 year) Pb-mAR transgenic mice were histologically normal, but Ki-67 immunostaining revealed marked increases in epithelial proliferation in ventral prostate and dorsolateral prostate. Older (>1 year) transgenic mice developed focal areas of intraepithelial neoplasia strongly resembling human high-grade prostatic intraepithelial neoplasia (PIN), a precursor to PCa. These results demonstrate that the AR is a positive regulator of cell growth in normal prostate epithelium and provide a model system of AR-stimulated PIN that can be used for assessing preventative hormonal therapies and for identifying secondary transforming events relevant to human PCa.
Links	PubMed PMC58558 Online version:10.1073/pnas.191235898
Keywords	Animals; Apoptosis; Epithelial Cells/cytology; Epithelial Cells/metabolism; Gene Expression; Male; Mice; Mice, Transgenic; Prostate/cytology; Prostatic Intraepithelial Neoplasia/metabolism; Prostatic Intraepithelial Neoplasia/pathology; Receptors, Androgen/biosynthesis; Receptors, Androgen/genetics; Transgenes
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ANDR	involved_in	GO:0060769: positive regulation of epithelial cell proliferation involved in prostate gland development	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:ANDR	acts_upstream_of_or_within	GO:0060769: positive regulation of epithelial cell proliferation involved in prostate gland development	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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