Open AccessExpression 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
Author(s) -
Altuwaijri Saleh,
Wu ChengChia,
Niu YuanJie,
Mizokami Atsushi,
Chang HongChiang,
Chang Chawnshang
Publication year - 2007
Publication title -
asian journal of andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 74
eISSN - 1745-7262
pISSN - 1008-682X
DOI - 10.1111/j.1745-7262.2007.00258.x
Subject(s) - androgen receptor , dihydrotestosterone , prostate cancer , cell growth , transfection , clone (java method) , biology , androgen , microbiology and biotechnology , cell culture , cancer research , chemistry , endocrinology , cancer , gene , biochemistry , genetics , hormone
Aim: 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. Methods: 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. Results: 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. Conclusion: 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.