Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: Hyper-activation 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, upon 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 co-deletion 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. To better assess the role of Phlpp in prostate we performed micorarray analysis of gene expression in the WT and Pten+/-; Phlpp1-/- mice.

ORGANISM(S): Mus musculus

SUBMITTER: Muhan Chen

PROVIDER: E-GEOD-30987 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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