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Submitted on July 27, 2005
Accepted on September 19, 2005
School of Molecular Biosciences, Center For Reproductive Biology, Bioinformatics Core Laboratory, Washington State University, Pullman, WA 99164
* To whom correspondence should be addressed. E-mail: jchaudhary{at}cau.edu.
A major hurdle in understanding the role of androgens is the heterogeneity of androgen receptor (AR) expression in the prostate. Since majority of prostate cancer arises from the AR+ve secretory luminal epithelial cells, hence identifying the androgen-mediated pathways in the prostate epithelium is of great significance to understand their role in prostate pathogenesis. To meet this objective, the current study was designed to identify immediate early genes expressed in response to synthetic androgen R1881 in cultured rat ventral prostate epithelial cells (rVPEC). The rVPEC, purified from 20day old rats were cultured and the presence of AR and response to androgen was established. The cells were then treated with R1881 for 2 and 12 h to capture immediate early genes in an Affymetrix based gene chip platform. A total of 66 non-redundant genes were identified that were responsive to R1881. The functional androgen response elements were identified in the proximal promoter to determine possible molecular mechanism. Cluster analysis identified 5 distinct signatures of R1881 induced genes. Pathway-analysis suggested that R1881 primarily influences cell proliferation/ differentiation and inflammatory/ immune response pathways. Androgens appear to regulate cell renewal by regulating differentiation, cell proliferation and apoptosis. Two mutually exclusive inflammatory response pathways were observed. The interferon pathway was unregulated and the interleukins were down regulated. The data identified novel androgen regulated genes (e.g. Id1, Id3, Il6, IGFBP2 and 3, JunB). Loss of androgen regulation of these genes can have important consequences for cellular transformation and transition to androgen independent growth and survival.
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