Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Transcription profiling by array of rat fibroblasts transformed with HRAS after treatment with 5-aza-2-deoxycytidine      
dateReleased:
11-06-2007
description:
Silencing of gene expression by methylation of CpG islands in regulatory elements is frequently observed in cancer. However, an influence of the most common oncogenic signalling pathways onto DNA methylation has not yet been investigated thoroughly. To address this issue, we identified genes suppressed in HRAS-transformed rat fibroblasts but up-regulated after treatment with the demethylating agent 5-Aza-CdR and with the MEK1,2 inhibitor U0126. Analysis of gene expression by microarray and Northern blot analysis revealed the MEK/ERK target genes clusterin, Mmp2, Ppicap, syndecan 4, Timp2, Thbs1 to be repressed in the HRAS-transformed FE-8 cells in a MEK/ERK- and in a methylation-dependent manner. Hypermethylation of putative regulatory elements in HRAS-transformed cells as compared to immortalized fibroblasts was detected within a CpG island 14.5 kb upstream of clusterin, within the clusterin promoter and within a CpG island of the Mmp2 promoter by bisulphite sequencing. Furthermore, hypermethylation of the clusterin promoter was observed ten days after induction of HRAS in immortalized rat fibroblasts and a clear correlation between reduced clusterin expression and hypermethlyation could also be observed in distinct rat tissues. These results suggest that silencing of individual genes by DNA methylation is controlled by oncogenic signalling pathways, yet the mechanisms responsible for initial target gene suppression are variable. Experiment Overall Design: Gene expression was analyzed in immortal (208F) and HRAS oncogene-transformed (FE8) rat fibroblasts after demethylation by 5-aza-2'-deoxycytidine. Genes potentially methylated in RAS-transformed cells were identified by bisulphite sequencing
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-4427
refinement:
raw
alternateIdentifiers:
4427
keywords:
functional genomics
dateModified:
03-08-2012
creators:
Christine Sers
availability:
available
types:
gene expression
name:
Rattus norvegicus
ID:
A-AFFY-18
name:
Affymetrix GeneChip Rat Genome U34A [RG_U34A]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-4427/E-GEOD-4427.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-4427/E-GEOD-4427.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4427
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
Similar Datasets

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.