A CELL-SPECIFIC AND SELECTIVE EFFECT ON TRANSACTIVATION BY THE ANDROGEN RECEPTOR

The androgen (AR) and glucocorticoid receptors (GR) are related ligand -activated transcriptional regulators which bind the same cis-acting e lement and are coexpressed in a variety of cell types. Despite a share d DNA binding site, these receptors mediate diverse cellular responses . To explain this paradox, the existence of cell-specific factors that interact with, and modulate the function of, distinct receptors has b een proposed. Prostate epithelial cell growth is sensitive to androgen s, but is not affected by glucocorticoids, even though both AR and GR are expressed in these cells. We have recently isolated a unique panel of prostate epithelial cell lines from normal rats and have used thes e cell lines to examine cell-specific steroid responses. In this study , we compared the abilities of AR and GR to enhance transcription of s everal different reporter genes regulated by simple (i.e., noncomposit e) hormone response elements (HREs) in prostate and nonprostate cell l ines. The cell-specific effect occurred independently of the AR hormon e binding domain and could be observed with a GAL4 fusion protein cont aining only the AR N-terminal regulatory domain. Gel shift analyses sh owed that the relative DNA binding affinity of AR for a probe containi ng a simple HRE was similar in prostate and nonprostate cell extracts. Presently, the only factors known to mediate steroid receptor-specifi c gene regulation are cJun and cFos, but there were no cell-specific d ifferences in the functional levels of these proteins which could acco unt for a preferential effect on AR-dependent transcription. Taken tog ether, these results suggest that cell-specific activities exist which can preferentially modulate transcriptional transactivation by AR. (C ) 1995 Academic Press, Inc.