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PMID:11535819

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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

Significance

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

Notes

See also

References

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