Androgen and its receptor promote Bax-mediated apoptosis
Androgen and its receptor promote Bax-mediated apoptosis
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DOI：
10.1128/mcb.26.5.1908-1916.2006
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Xiang, JL
中科院分区：
文献类型：
--
作者：
Lin, YT;Kokontis, J;Xiang, JL
据报道，雄激素及其受体（AR）具有促或抗凋亡功能。然而，其潜在的分子机制尚不完全清楚。我们在此报道雄激素和AR促进bax介导的前列腺癌细胞凋亡。紫外线照射和Bax的异位表达诱导ar阳性前列腺癌细胞凋亡，而ar阴性前列腺癌细胞凋亡不发生。在表达AR小干扰RNA （siRNA）的AR阳性细胞中，UV和bax诱导的凋亡被消除，并通过将AR重新引入AR阴性细胞而致敏。虽然AR能够独立于雄激素促进bax介导的细胞凋亡，但雄激素可以通过AR依赖的转录激活进一步增强AR的促进作用。在UV-或Bax诱导的细胞凋亡中，AR对于Bax向线粒体的易位至关重要。Bax siRNA抑制Bax表达可抑制uv诱导的ar阳性细胞凋亡。此外，AR导入AR阴性前列腺癌细胞可上调BH3-only蛋白Noxa的表达水平，而抑制Noxa表达可降低AR对紫外线诱导的细胞凋亡的促进作用。因此，我们的研究结果揭示了雄激素/AR激素信号通路与内在凋亡死亡通路之间的一种新的串扰，这种串扰决定了应激诱导前列腺癌细胞凋亡的敏感性。
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.