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Endogenous tumor suppression mediated by PTEN involves survivin gene silencing.

Authors
  • Guha, Minakshi
  • Plescia, Janet
  • Leav, Irwin
  • Li, Jing
  • Languino, Lucia R
  • Altieri, Dario C
Type
Published Article
Journal
Cancer Research
Publisher
American Association for Cancer Research
Publication Date
Jun 15, 2009
Volume
69
Issue
12
Pages
4954–4958
Identifiers
DOI: 10.1158/0008-5472.CAN-09-0584
PMID: 19470765
Source
Medline
License
Unknown

Abstract

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.

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