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Status |
Public on Aug 01, 2012 |
Title |
Hierarchical regulation in a KRAS pathway-dependent transcriptional network revealed by a reverse-engineering approach (7TF and control) |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by array
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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.
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Overall design |
RAS-ROSE cells were treated with siRNA against 7 transcription factors or controls,
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Contributor(s) |
Stelniec I, Schäfer R, Blüthgen N |
Citation(s) |
22864383 |
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Submission date |
Jun 07, 2012 |
Last update date |
Aug 10, 2012 |
Contact name |
Nils Blüthgen |
E-mail(s) |
nils.bluethgen@charite.de
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Organization name |
Charite Universitätsmedizin Berlin
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Department |
Institute of Pathology
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Street address |
Chariteplatz 1
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City |
Berlin |
ZIP/Postal code |
10117 |
Country |
Germany |
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Platforms (1) |
GPL10741 |
[RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [probe set (exon) version] |
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Samples (16)
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GSM945778 |
RAS-ROSE cells treated with transfection reagents only |
GSM945779 |
RAS-ROSE cells treated with Scrambled siRNA |
GSM945780 |
RAS-ROSE cells treated with Otx1 siRNA 1 |
GSM945781 |
RAS-ROSE cells treated with Otx1 siRNA 2 |
GSM945782 |
RAS-ROSE cells treated with Gfi1 siRNA 1 |
GSM945783 |
RAS-ROSE cells treated with Gfi1 siRNA 2 |
GSM945784 |
RAS-ROSE cells treated with RelA siRNA 1 |
GSM945785 |
RAS-ROSE cells treated with RelA siRNA 2 |
GSM945786 |
RAS-ROSE cells treated with Klf6 siRNA 1 |
GSM945787 |
RAS-ROSE cells treated with Klf6 siRNA 2 |
GSM945788 |
RAS-ROSE cells treated with JunB siRNA 1 |
GSM945789 |
RAS-ROSE cells treated with JunB siRNA 2 |
GSM945790 |
RAS-ROSE cells treated with Fosl1 siRNA 1 |
GSM945791 |
RAS-ROSE cells treated with Fosl1 siRNA 2 |
GSM945792 |
RAS-ROSE cells treated with Hmga2 siRNA 1 |
GSM945793 |
RAS-ROSE cells treated with Hmga2 siRNA 2 |
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This SubSeries is part of SuperSeries: |
GSE38614 |
Hierarchical regulation in a KRAS pathway-dependent transcriptional network revealed by a reverse-engineering approach |
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Relations |
BioProject |
PRJNA168232 |