title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Saleh
authors.initials: S
authors.lastname: Altuwaijri
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Wu
authors.forename: Yuan-Jie
authors.initials: YJ
authors.lastname: Niu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.forename: Hong-Chiang
authors.initials: HC
authors.lastname: Chang
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000494:pharmacology; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D011944:Receptors, Androgen; D013196:Dihydrotestosterone