NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss

被引：139

作者：

Lei, Qunying

Jiao, Jing

Xin, Li

Chang, Chun-Ju

Wang, Shunyou

Gao, Jing

Gleave, Martin E.

Witte, Owen N.

Liu, Xin

Wu, Hong ^{[1
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[5] Vancouver Gen Hosp, Prostate Ctr, Vancouver, BC V6H 3Z6, Canada

来源：

CANCER CELL | 2006年 / 9卷 / 05期

关键词：

D O I：

10.1016/j.ccr.2006.03.031

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We demonstrate that PTEN loss causes reduced NKX3.1 expression in both murine and human prostate cancers. Restoration of Nkx3.1 expression in vivo in Pten null epithelium leads to decreased cell proliferation, increased cell death, and prevention of tumor initiation. Whereas androgen receptor (AR) positively regulates NKX3.1 expression, NKX3.1 negatively modulates AR transcription and consequently the AR-associated signaling events. Consistent with its tumor suppressor functions, NKX3.1 engages cell cycle and cell death machinery via association with HDAC1, leading to increased p53 acetylation and half-life through MDM2-dependent mechanisms. Importantly, overexpression of Nkx3.1 has little effect on Pten wild-type epithelium, suggesting that PTEN plays a predominant role in PTEN-NKX3.1 interplay. Manipulating NKX3.1 expression may serve as a therapeutic strategy for treating PTEN-deficient prostate cancers.

引用

页码：367 / 378

页数：12

共 53 条

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