Differential regulation of steroid nuclear receptor coregulator expression between normal and neoplastic prostate epithelial cells

Deregulated androgen receptor (AR) action is critical for prostate cancer (PCa) progression. Aberrant expression of AR-associated coregulators contributes to AR activity in PCa. The mechanisms underlying coregulator expression in PCa are under intense investigation as they may lead to alternative means of targeting AR activity in PCa cells. We have recently shown that over 30% of coregulator expression in the PCa cell line LNCaP is subject to androgen regulation.

Our data indicate differences in the regulation of coregulator expression between neoplastic and normal prostate cells. These findings emphasize the important potential of targeting the mechanisms regulating coregulator expression for therapeutic intervention in PCa.

Using multiple PCa cell lines as well as xenograft models, non-malignant prostate epithelial cell lines and androgen-responsive tissues derived from a male Wistar rat model system, we explored the effect of androgen stimulation and androgen deprivation on the expression of the core coactivators SRC1, SRC2, SRC3, CBP, and p300.

Androgen stimulation of model systems representing PCa led to a decrease in the expression of SRC1, SRC2, SRC3, CBP, and p300, whereas androgen deprivation induced the expression of these coactivators. In contrast, expression of these coregulators remained largely unaffected following changes in the androgenic milieu in AR-positive models representing non-malignant prostate cells and tissues. Conclusions: Our data indicate differences in the regulation of coregulator expression between neoplastic and normal prostate cells. These findings emphasize the important potential of targeting the mechanisms regulating coregulator expression for therapeutic intervention in PCa.