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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 17, 2011 |
| Title |
Identification of PHLPP1 as a tumor suppressor reveals the role of feedback compensation in PTEN-mutant prostate cancer progression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
To better assess the role of Phlpp in prostate we performed micorarray analysis of gene expression in the WT and Pten+/-; Phlpp1-/- mice.
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| Contributor(s) |
Chen M, Pratt CP, Zeeman ME, Schultz N, Taylor BS, O'Neill A, Castillo-Martin M, Nowak DG, Naguib A, Grace DM, Murn J, Navin N, Atwal GS, Sander C, Gerald WL, Cordon-Cardo C, Newton AC, Carver BS, Trotman LC |
| Citation(s) |
21840483 |
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| Submission date |
Jul 27, 2011 |
| Last update date |
Aug 27, 2019 |
| Contact name |
Muhan Chen |
| Organization name |
Cold Spring Harbor Laboratory
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| Street address |
1 Bungtown Rd
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| City |
Cold Spring Harbor |
| ZIP/Postal code |
11724 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| GSM780865 |
Wild type, 4 month timepoint, replicate 1 |
| GSM780866 |
Wild type, 4 month timepoint, replicate 2 |
| GSM780867 |
Wild type, 4 month timepoint, replicate 3 |
| GSM780868 |
Wild type, 6 month timepoint, replicate 1 |
| GSM780869 |
Wild type, 6 month timepoint, replicate 2 |
| GSM780870 |
Wild type, 6 month timepoint, replicate 3 |
| GSM780871 |
Pten/Phlpp double mutant, 4 month timepoint, replicate 1 |
| GSM780872 |
Pten/Phlpp double mutant, 6 month timepoint, replicate 1 |
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| Relations |
| BioProject |
PRJNA146201 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30987_RAW.tar |
35.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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