Androgen receptor drives cellular senescence.
Androgen receptor drives cellular senescence.
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DOI：
10.1371/journal.pone.0031052
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Volpert OV
中科院分区：
文献类型：
--
作者：
Mirochnik Y;Veliceasa D;Williams L;Maxwell K;Yemelyanov A;Budunova I;Volpert OV
The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.
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DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
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通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
Kazanietz, Marcelo G.
影响因子：
11.2
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通讯作者：
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DOI：
10.1016/j.jsbmb.2005.04.029
发表时间：
2005-08-01
影响因子：
4.1
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
La Mantia, G