Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression Journal Article

   

Authors:	Chen, M.; Pratt, C.; Zeeman, M.; Schultz, N.; Taylor, B.; O'neill, A.; Castillo-Martin, M.; Nowak, D.; Naguib, A.; Grace, D.; Murn, J.; Navin, N.; Atwal, G.; Sander, C.; Gerald, W.; Cordon-Cardo, C.; Newton, A.; Carver, B.; Trotman, L.
Article Title:	Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression
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. © 2011 Elsevier Inc.
Keywords:	controlled study; human tissue; unclassified drug; gene deletion; cancer growth; nonhuman; protein analysis; mouse; animal tissue; metastasis; protein p53; prostate cancer; genome analysis; genetic engineering; nucleotide sequence; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; cell membrane; gene loss; senescence; tumor suppressor protein; conceptual framework; tumor suppressor protein phlpp1; tumor suppressor protein phlpp2
Journal Title:	Cancer Cell
Volume:	20
Issue:	2
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2011-08-16
Start Page:	173
End Page:	186
Language:	English
DOI:	10.1016/j.ccr.2011.07.013
PROVIDER:	scopus
PMCID:	PMC3176728
PUBMED:	21840483
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80051579092&partnerID=40&md5=931e8406ed3008aee9f6be9f626bf778
Notes:	--- - "Export Date: 3 October 2011" - "CODEN: CCAEC" - "Source: Scopus"

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