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E-GEOD-27932 - FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis

Status
Released on 16 March 2011, last updated on 27 March 2012
Organism
Mus musculus
Samples (14)
Array (1)
Protocols (6)
Description
Activated phosphoinositide 3-kinase (PI3K)-AKT signaling appears to be an obligate event in the development of cancer. The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the role of FoxOs in the neoplastic phenotypes linked to PI3K-AKT activation. While germline or somatic deletion of up to five FoxO alleles produced remarkably modest neoplastic phenotypes, broad somatic deletion of all FoxOs engendered a progressive cancer-prone condition characterized by thymic lymphomas and hemangiomas, demonstrating that the mammalian FoxOs are indeed bona fide tumor suppressors. Transcriptome and promoter analyses of differentially affected endothelium identified direct FoxO targets and revealed that FoxO regulation of these targets in vivo is highly context-specific, even in the same cell type. Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis. Mice were engineered with negative control (MxCre- Fk1 L/L Fk2 L/L Afx L/L) and experimental (MxCre+ Fk1 L/L Fk2 L/L Afx L/L) genotypes. RNAs were isolated from Lung endothelial cells (2 negative controls, 2 experimental), liver sinusoidal endothelial cells (3 negative controls, 3 experimental) and thymus cells (2 negative controls, 2 experimental), and profiled on Affymetrix Mouse Genome 430 2.0 Array.
Experiment type
transcription profiling by array 
Contacts
Daniel R Carrasco, Diego H Castrillon, Gary Gilliland, Gerald Chu, Hongkai Ji, James W Horner, Ji-Hye Paik, Lili Miao, Lynda Chin, Ramya Kollipara, Ronald A DePinho, Shan Jiang, Wing H Wong, Yonghong Xiao, Zhihu Ding, Zuzana Tothova
Citation
FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Paik JH, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, Miao L, Tothova Z, Horner JW, Carrasco DR, Jiang S, Gilliland DG, Chin L, Wong WH, Castrillon DH, DePinho RA. , PMID:17254969
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-27932.idf.txt
Sample and data relationshipE-GEOD-27932.sdrf.txt
Raw data (1)E-GEOD-27932.raw.1.zip
Processed data (1)E-GEOD-27932.processed.1.zip
Array designA-AFFY-45.adf.txt
R ExpressionSetE-GEOD-27932.eSet.r
Links