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Title: A Transcriptional Signature and Common Gene Networks Link Cancer with Metabolic Syndrome and Auto-immune Diseases      
dateReleased:
04-19-2010
description:
Epidemiological studies have revealed concurrence of specific cancers with other disease states such as metabolic syndrome, inflammatory disease and autoimmune disease. Patients with these chronic conditions have a higher incidence of various cancers, more aggressive tumors, and a higher mortality rate. It has been proposed that obesity, inflammation and chronic disease should be correlated with cancer at the molecular level, but common gene signatures or networks have yet to be described. Here, we identify genes regulated during the process of cellular transformation in both a breast epithelial cell line and a set of isogenic fibroblastic cell lines. The resulting gene signature strongly mimics those of many different cancer types, thereby validating these experimental systems as models of oncogenesis. Furthermore, it uncovers transcriptional factors and common gene regulatory networks linking cancer with other disease states such as atheroscelorsis, type II diabetes, obesity, lupus, and cardiomyopathy. We suggest that this common transcriptional program can contribute to the concurrence of different diseases, and that the interplay between this program and cell-type specific factors can give rise to a variety of human diseases. Two isogenic cell lines were used to model transformation. The first employed an inducible oncogene: src fused to the ligand binding domain of the estrogen receptor. ER-src and pBABE control cells were dosed with Tamoxifen or Etoh control across several time points to monitor gene expression during transformation. The other model consists of three isogenic cell lines derived from primary fibroblasts in a serial manner. The first is immortalized by overexpression of telomerase (hTERT), and exhibits normal fibroblast morphology. The second expresses hTERT along with both large and small T antigens of Simian virus 40, and it displays an altered morphology but is not transformed. The third cell line expresses hTERT, T antigens, and an oncogenic derivative of Ras (H-RasV12); it is morphologically transformed and has tumorigenic potential in soft agar and nude mice. Thus, three stages of transformation are represented by these cells.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-17941
refinement:
raw
alternateIdentifiers:
17941
keywords:
functional genomics
dateModified:
03-27-2012
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-9188
name:
Affymetrix GeneChip Human Genome U133A 2.0 Array [CDF: Brainarray Version 10, Hs133Av2_Hs_ENTREZG]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-17941/E-GEOD-17941.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-17941/E-GEOD-17941.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=GSE17941
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
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