Endogenous Tumor Suppression Mediated by PTEN Involves Survivin Gene Silencing

被引：58

作者：

Guha, Minakshi ^{[1
]}

Plescia, Janet ^{[1
]}

Leav, Irwin ^{[1
]}

Li, Jing ^{[1
]}

Languino, Lucia R. ^{[1
]}

Altieri, Dario C. ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Canc Biol, Prostate Canc Discovery & Dev Program, Worcester, MA 01605 USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 12期

关键词：

WILD-TYPE P53; PROSTATE-CANCER; COLON-CANCER; EXPRESSION; PATHWAY; APOPTOSIS; BRAIN; CELLS;

D O I：

10.1158/0008-5472.CAN-09-0584

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Endogenous tumor suppression provides a barrier against oncogenesis, but the molecular requirements of this process are not well understood. Here, we show that the dual specificity phosphatase PTEN, a gene almost universally altered in human tumors, silences the expression of survivin, an essential regulator of cell division and apoptosis in cancer. This pathway is independent of p53, involves active repression of survivin gene transcription, and is mediated by direct occupancy of the survivin promoter by FOXO1 and FOXO3a factors. Conditional deletion of PTEN in the mouse prostate causes deregulated induction of survivin before full-blown transformation in vivo, whereas expression of survivin and PTEN is inversely correlated in cancer patients. Therefore, silencing the survivin gene is an essential requirement of endogenous PTEN tumor suppression.[Cancer Res 2009;69(12):4954-8]

引用

页码：4954 / 4958

页数：5

共 20 条

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