title: Phenethyl isothiocyanate inhibits androgen receptor-regulated transcriptional activity in prostate cancer cells through suppressing PCAF.
abstract: METHODS
  Androgen receptor (AR) signaling is critical for all aspects of prostate growth and tumorigenesis. The glucosinolate-derived phenethyl isothiocyanate (PEITC) has recently been demonstrated to reduce the risk of prostate cancer (PCa) and inhibit PCa cell growth. We previously reported that p300/CBP-associated factor (PCAF), a co-regulator for AR, is upregulated in PCa cells through suppression of the mir-17 gene. Here, we assessed the effects of PEITC on PCAF expression and AR-regulated transcriptional activity in PCa cells.
  
  
  RESULTS
  Using AR-responsive LNCaP cells, we observed the inhibitory effects of PEITC on the dihydrotestosterone-stimulated AR transcriptional activity and cell growth of PCa cells. Interestingly, overexpression of PCAF attenuated the inhibitory effects of PEITC on dihydrotestosterone-stimulated AR transcriptional activity. Expression of PCAF was upregulated in PCa cells through suppression of miR-17. PEITC treatment significantly decreased PCAF expression and promoted transcription of miR-17 in LNCaP cells. Functional inhibition of miR-17 attenuated the suppression of PCAF in cells treated by PEITC.
  
  
  CONCLUSIONS
  Our results indicate that PEITC inhibits AR-regulated transcriptional activity and cell growth of PCa cells through miR-17-mediated suppression of PCAF, suggesting a new mechanism by which PEITC modulates PCa cell growth.
authors: Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE, USA; Department of Clinical Nursing, School of Nursing, Beijing University of Chinese Medicine, Beijing, P. R. China.
authors: Chunguang
authors: C
authors: Yu
authors: Ai-Yu
authors: AY
authors: Gong
authors: Dongqing
authors: D
authors: Chen
authors: Daniel
authors: D
authors: Solelo Leon
authors: Charles Y F
authors: CY
authors: Young
authors: Xian-Ming
authors: XM
authors: Chen
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D015854:Up-Regulation; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D013196:Dihydrotestosterone; D017879:Isothiocyanates; D035683:MicroRNAs; D011944:Receptors, Androgen; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C410798:AR protein, human; C524941:MIRN17 microRNA, human; C058305:phenethyl isothiocyanate
keywords: Androgen receptor; Phenethyl isothiocyanate; Prostate cancer; miR-17; p300/CBP-associated factor