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Series GSE38585 Query DataSets for GSE38585
Status Public on Aug 01, 2012
Title Hierarchical regulation in a KRAS pathway-dependent transcriptional network revealed by a reverse-engineering approach (RAS-ROSE and ROSE with siRNA)
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
 
Overall design RAS-ROSE cells and ROSE cells treated with Scrambled siRNA
 
Contributor(s) Stelniec I, Schäfer R, Blüthgen N
Citation(s) 22864383
Submission date Jun 07, 2012
Last update date Aug 10, 2012
Contact name Nils Blüthgen
E-mail(s) nils.bluethgen@charite.de
Organization name Charite Universitätsmedizin Berlin
Department Institute of Pathology
Street address Chariteplatz 1
City Berlin
ZIP/Postal code 10117
Country Germany
 
Platforms (1)
GPL10741 [RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [probe set (exon) version]
Samples (2)
GSM945794 RAS-ROSE cells treated with scrambled siRNA
GSM945795 ROSE cells treated with scrambled siRNA
This SubSeries is part of SuperSeries:
GSE38614 Hierarchical regulation in a KRAS pathway-dependent transcriptional network revealed by a reverse-engineering approach
Relations
BioProject PRJNA168226

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE38585_RAW.tar 8.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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