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Title: Induction of hepatocellular carcinoma through activation of stromal cells in Pdgf-c transgenic mice      
dateReleased:
05-12-2014
description:
Liver cirrhosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet the mechanisms by which cirrhosis predisposes patients to tumorigenesis are not well understood. Transgenic mice expressing platelet-derived growth factor C (Pdgf-c) under the control of the albumin promoter provide a unique animal model that mimics the step-wise disease progression in humans from fibrosis to HCC. The livers of Pdgf-c Tg mice show evidence of liver injury, including inflammation, proliferation, fibrosis and steatosis, and as the mice age, angiogenesis and dysplasia. Eighty-five percent of these mice develop HCC spontaneously, and have reduced survival that is related to their liver pathology. Through measurement of protein, RNA, and histological markers, we provide evidence to support the hypothesis that changes in liver stromal cells play an essential role in tumorigenesis in this model. A paracrine signaling model is proposed where ectopic expression of Pdgf-c in hepatocytes results in activation of hepatic stellate cells, which subsequently activates endothelial and Kupffer cells. Activation of these non-parenchymal cells promotes the release of hepatocyte growth factors that, together with changes in extracellular matrix, lead to the formation of HCC. Pdgf-c Tg mice provide a useful pre-clinical model in which to test novel drugs for chronic liver disease and HCC that focus on blocking the processes that alter the liver's fibrotic microenvironment. Two strains of mice, C57BL/6 and C57/BL6 Pdgf-c transgenic, were analyzed to see if liver stromal cells play an essential role in tumorigenesis.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-38199
refinement:
raw
alternateIdentifiers:
38199
keywords:
functional genomics
dateModified:
05-19-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-AFFY-130
name:
Affymetrix GeneChip Mouse Gene 1.0 ST Array [MoGene-1_0-st-v1]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-38199/E-GEOD-38199.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-38199/E-GEOD-38199.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=GSE38199
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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