| Literature DB >> 21840483 |
Muhan Chen1, Christopher P Pratt, Martha E Zeeman, Nikolaus Schultz, Barry S Taylor, Audrey O'Neill, Mireia Castillo-Martin, Dawid G Nowak, Adam Naguib, Danielle M Grace, Jernej Murn, Nick Navin, Gurinder S Atwal, Chris Sander, William L Gerald, Carlos Cordon-Cardo, Alexandra C Newton, Brett S Carver, Lloyd C Trotman.
Abstract
Hyperactivation of the PI 3-kinase/AKT pathway is a driving force of many cancers. Here we identify the AKT-inactivating phosphatase PHLPP1 as a prostate tumor suppressor. We show that Phlpp1-loss causes neoplasia and, on partial Pten-loss, carcinoma in mouse prostate. This genetic setting initially triggers a growth suppressive response via p53 and the Phlpp2 ortholog, and reveals spontaneous Trp53 inactivation as a condition for full-blown disease. Surprisingly, the codeletion of PTEN and PHLPP1 in patient samples is highly restricted to metastatic disease and tightly correlated to deletion of TP53 and PHLPP2. These data establish a conceptual framework for progression of PTEN mutant prostate cancer to life-threatening disease.Entities:
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Year: 2011 PMID： 21840483 PMCID： PMC3176728 DOI： 10.1016/j.ccr.2011.07.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743