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Series GSE7562 Query DataSets for GSE7562
Status Public on Jun 01, 2007
Title Identification of the JNK Signaling Pathway as a Functional Target of the Tumor Suppressor PTEN
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Although most of the oncogenic phenotypes of PTEN loss have been attributed to AKT activation, AKT alone is not sufficient to induce all of the biological activities associated with PTEN inactivation. We searched for additional PTEN-regulated pathways through gene set enrichment analysis (GSEA) and found that PTEN inactivation causes an enrichment of genes associated with JNK activation. Biochemically, PTEN-null cells exhibit higher JNK activity, and genetic studies demonstrate that JNK functions parallel to and independently of AKT. Furthermore, PTEN deficiency sensitizes cells to JNK inhibition. We also found that negative feedback regulation of PI3K was impaired in PTEN-null cells. These findings implicate JNK in PI3K-driven cancers and demonstrate the utility of GSEA to identify functional pathways using genetically defined systems.
Keywords: Genetic modification: PTEN RNAi
 
Overall design A431, HCC827 and SKBR-3 cells were retrovirally and stably transduced with a small hairpin RNA targeting human PTEN. PTEN knockdown was confirmed at the protein level by western blot to be approximately 90%. PTEN-deficient sublines were named by adding the suffix "PR"(for PTEN RNAi) at the end of each of the parental cell line names. For example, PTEN deficient A431 cells are called A431-PR. RNA was extracted from each of the parental and PTEN-deificient lines. Each sample was done in duplicate (ie two chips per sample) for a total of twelve samples.
 
Contributor(s) Vivanco I, Palaskas NJ, Tran C, Finn SP, Getz G, Kennedy NJ, Jiao J, Rose J, Xie W, Loda M, Golub T, Mellinghoff IK, Davis RJ, Wu H, Sawyers CL
Citation(s) 17560336
Submission date Apr 20, 2007
Last update date Jan 08, 2019
Contact name Igor Vivanco
E-mail ivivanco@ucla.edu
Phone (310) 825 1205
Fax (310) 206 8975
Organization name UCLA
Department Mol. & Md. Pharmacology
Lab Mellinghoff
Street address 700 Westwood plaza
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (12)
GSM183432 A431 WT 1
GSM183433 A431 WT 2
GSM183434 A431 PR 1
Relations
BioProject PRJNA100359

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Supplementary file Size Download File type/resource
GSE7562_RAW.tar 60.2 Mb (http)(custom) TAR (of CEL, CHP)
Raw data provided as supplementary file
Processed data provided as supplementary file

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