Expression of human AR cDNA driven by its own promoter results in mild promotion, but not suppression, of growth in human prostate cancer PC-3 cells / 亚洲男科学杂志(英文版)

ABSTRACT

<p><b>AIM</b>To examine the physiological role of the androgen receptor (AR) in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter.</p><p><b>METHODS</b>We generated an AR-expressing PC-3(AR)9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3(AR)2 (stable clone that expresses AR under the control of the cytomegalovirus (CMV) promoter, established by Heisler et al.) after androgen treatment.</p><p><b>RESULTS</b>We found that dihydrotestosterone (DHT) from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3(AR)2 compared with its vector control, PC-3(pIRES). In contrast, PC-3(AR)9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT.</p><p><b>CONCLUSION</b>These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer (AIPC) PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3(AR)9 prostate cancer cells.</p>