Androgen and its receptor promote Bax-mediated apoptosis.
Mol Cell Biol
; 26(5): 1908-16, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16479009
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Androgênicos
/
Apoptose
/
Proteína X Associada a bcl-2
/
Androgênios
Limite:
Humans
/
Male
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos