DEN-induced HCC in c-Met knockout mice
Transcriptomics Dataset
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General Information
AccessionGSE8747
TitleDEN-induced HCC in c-Met knockout mice
DescriptionHGF has been reported to have both positive and negative effects on carcinogenesis. Here we show that the loss of c-Met signaling in hepatocytes enhanced rather than suppressed the early stages of chemical hepatocarcinogenesis. c-Met conditional knockout mice (c-metfl/fl, AlbCre+/-; MetLivKO) treated with N-nitrosodiethylamine (DEN) developed significantly more and bigger tumors and with a shorter latency as compared with control (wt/wt, AlbCre+/-; Cre-Ctrl) mice. Accelerated tumor development was associated with increased rate of cell proliferation and prolonged activation of epidermal growth factor receptor (EGFR) signaling. MetLivKO livers treated with DEN also displayed elevated lipid peroxidation, decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), and upregulation of superoxide dismutase 1 (Sod1) and heat shock protein 70 (Hsp70), all consistent with increased oxidative stress. Likewise, gene expression profiling performed at 3 and 5 months after DEN treatment revealed upregulation of genes associated with cell proliferation and stress responses in c-Met mutant livers. The negative effects of c-Met-deficiency were reversed by chronic oral administration of anti-oxidant N-acetylcysteine (NAC). NAC blocked the EGFR activation and reduced the DEN-initiated hepatocarcinogenesis to the levels of Cre-Ctrl mice. These results argue that intact HGF/c-Met signaling is essential for maintaining normal redox homeostasis in the liver and has tumor suppressor effect(s) during the early stages of DEN-induced hepatocarcinogenesis. Keywords: compound treatment design
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8747
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Cell Type
Geneset
Small molecules which mimic MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Small molecules which mimic MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MET knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in MET knockout
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes dysregulated in MET knockout
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
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