Simultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-κB activation and invasive prostate carcinoma

被引：28

作者：

Fernandez-Marcos, Pablo J. ^{[2
]}

Abu-Baker, Shadi ^{[1
]}

Joshi, Jayashree ^{[1
]}

Galvez, Anita ^{[1
]}

Castilla, Elias A. ^{[1
]}

Canamero, Marta ^{[2
]}

Collado, Manuel ^{[2
]}

Saez, Carmen ^{[3
]}

Moreno-Bueno, Gema ^{[2
]}

Palacios, Jose ^{[3
]}

Leitges, Michael ^{[4
]}

Serrano, Manuel ^{[2
]}

Moscat, Jorge ^{[1
]}

Diaz-Meco, Maria T. ^{[1
]}

机构：

[1] Univ Cincinnati, Coll Med, Dept Canc & Cell Biol, Cincinnati, OH 45267 USA

[2] Spanish Natl Canc Res Ctr, Madrid 28029, Spain

[3] Univ Hosp Virgen del Rocio, Seville 41013, Spain

[4] Univ Oslo, Ctr Biotechnol, N-0317 Oslo, Norway

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 31期

基金：

美国国家卫生研究院;

关键词：

AKT; aPKC; IL-6; inflammation; prostate cancer; TUMOR-SUPPRESSION; CANCER DEVELOPMENT; CELL-SURVIVAL; AKT; PATHWAY; TUMORIGENESIS; APOPTOSIS; KINASE; MOUSE; PROLIFERATION;

D O I：

10.1073/pnas.0813055106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Prostate cancer is one of the most common neoplasias in men. The tumor suppressor Par-4 is an important negative regulator of the canonical NF-kappa B pathway and is highly expressed in prostate. Here we show that Par-4 expression is lost in a high percentage of human prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 ( PTEN) loss. Par-4 null mice, similar to PTEN-heterozygous mice, only develop benign prostate lesions, but, importantly, concomitant Par-4 ablation and PTEN-heterozygosity lead to invasive prostate carcinoma in mice. This strong tumorigenic cooperation is anticipated in the preneoplastic prostate epithelium by an additive increase in Akt activation and a synergistic stimulation of NF-kappa B. These results establish the cooperation between Par-4 and PTEN as relevant for the development of prostate cancer and implicate the NF-kappa B pathway as a critical event in prostate tumorigenesis.

引用

页码：12962 / 12967

页数：6

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