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E-GEOD-18232

Title: RAS signaling in colon carcinoma: Target gene deregulation and growth control through Y-box-binding protein 1
Organism(s): Homo sapiens
Description: 3 colon cancer cell lines treated with sulindac sulfide, sulindac sulfone, or other chemicals. [original description: The perturbation of the genetic program due to mutational activation of KRAS- or BRAF-mediated signal transduction is a prerequisite for the expression of neoplastic phenotypes; however, the mechanisms of cancer cell-specific transcriptional deregulation are poorly understood. We have analyzed the human colorectal cancer cell lines HCT116, HT29 and SW480 using an integrated approach combining transcriptional profiling, small molecule inhibitors targeting signaling pathway effectors, and computational prediction of regulatory elements in promoters of co-expressed genes with chromatin-based and cellular assays. We identified groups of coexpressed genes involved in similar biological processes, demonstrating a link between biological function and transcriptional organization. Among them we found groups of proliferation associated genes which responded to MEK/MAPK inhibition in all three cell lines. We predicted by computational analysis of the promoter regions of these genes, that NFY binding sites might be important regulatory elements for the MEK/MAPK-dependent transcriptional control. We validated this prediction in reporter gene assays by using a fragment of the CCNB1 promoter as a model. We discovered YBX1 to be associated with the endogenous CCNB1 promoter and the promoters of 62 additional genes within the proliferation associated gene groups by a ChIP-on-chip assay. Silencing of YBX1 expression by siRNA prevents CCNB1 expression and partially inhibits proliferation of HCT116 cells. In view of multiple known YBX1 functions in stress response, chromatin remodeling, transcriptional and translational regulation, our results indicate that this factor may also contribute to RAS-induced pleiotropic effects in cancer. The cells were treated with certain inhibitors for 48 hours. We used one sample per cell line treated with DMSO as a control, and one sample for each of the treatments.]
Design(s): transcription profiling by array
Experimental factor(s):
cell line
3 recorded
HCT116 SW480 HT29
genotype
2 recorded
pseudo diploid aneuploid
Publication(s):
PubMed:21170361

Sample attribute(s):
control
1 recorded
condition
Material Type
1 recorded
total RNA
treatment duration
1 recorded
48 hour
cell line
3 recorded
HCT116 SW480 cell HT29 Cells
treatment
6 recorded
sulindac sulfone sulindac sulfide dimethyl sulfoxide 2-(2-amino-3-methoxyphenyl)chromen-4-one tyrphostin AG 1478 (2Z,3Z)-bis{amino(2-aminophenyl)sulfanylmethylidene}butanedinitrile
age
1 recorded
pass not known
tissue type
1 recorded
colorectal cancer cell
Label
1 recorded
biotin
genotype
2 recorded
pseudo diploid aneuploid
organism
1 recorded
Homo sapiens
Contact(s): Karsten JrchottReinhold SchferKarsten Jrchott
Release Date: 10/9/2010
Submission Date:
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Assay Downloads
transcription profiling using DNA microarray
18 assays