Androgen and its receptor promote Bax-mediated apoptosis.
Androgen and its receptor (AR) have been reported to have pro- or antiapoptotic functions. However, the underlying molecular mechanism is incompletely understood. We report here that androgen and AR promote Bax-mediated apoptosis in prostate cancer cells. UV irradiation and ectopic expression of Bax induce apoptosis in AR-positive, but not AR-negative prostate cancer cells. UV- and Bax-induced apoptosis is abrogated in AR-positive cells that express small interference RNA (siRNA) of AR and is sensitized by reintroduction of AR into AR-negative cells. Although AR is able to promote Bax-mediated apoptosis independently of androgen, the promotion by AR can be further potentiated by androgen via AR-dependent transcription activation. AR is essential for the translocation of Bax to mitochondria in UV- or Bax-induced apoptosis. Inhibition of Bax expression by Bax siRNA suppresses UV-induced apoptosis in AR-positive cells. In addition, introduction of AR into AR-negative prostate cancer cells upregulates expression levels of the BH3-only protein Noxa, whereas inhibition of Noxa expression reduces the promotion by AR on UV-induced apoptosis. Thus, our results reveal a novel cross talk between the androgen/AR hormonal signaling pathway and the intrinsic apoptotic death pathway that determines the sensitivity of stress-induced apoptosis in prostate cancer cells.
Department of Biological, Chemical, and Physical Science, Illinois Institute of Technology, Chicago, IL 60616, USA.
Yuting
Y
Lin
John
J
Kokontis
Fangming
F
Tang
Bradley
B
Godfrey
Shutsung
S
Liao
Anning
A
Lin
Youting
Y
Chen
Jialing
J
Xiang
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D014105:Tosyl Compounds; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; C494826:BAX protein, human; D009570:Nitriles; C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D051028:bcl-2-Associated X Protein; D015741:Metribolone; C053541:bicalutamide