期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：31
页码：12962-12967
DOI：10.1073/pnas.0813055106
语种：English
出版社：The National Academy of Sciences of the United States of America
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.
关键词：AKT ; aPKC ; IL-6 ; inflammation ; prostate cancer
