Mouse models of hepatocellular carcinoma (HCC) simulate specific subgroups of human HCC. We investigated hepatocarcinogenesis in Mdr2-KO mice, a model of inflammation-associated HCC, using gene expression profiling and immunohistochemical analyses. Gene expression profiling demonstrated that although Mdr2-KO mice differ from other published murine HCC models, they share several important deregulated pathways and many coordinately differentially expressed genes with human HCC datasets. Analysis of genome positions of differentially expressed genes in liver tumors revealed a prolonged region of down-regulated genes on murine chromosome 8 in three of the six analyzed tumor samples. This region is syntenic to human chromosomal regions that are frequently deleted in human HCC and harbor multiple tumor suppressor genes. Real-time RT-PCR analysis of 16 tumor samples confirmed down-regulation of several tumor suppressors in most tumors. We demonstrate that in the aged Mdr2-KO mice, cyclin D1 nuclear level is increased in dysplastic hepatocytes that do not form nodules; however, it is decreased in dysplastic nodules and in liver tumors. We found that this decrease is mostly at the protein, rather than the mRNA level. These findings raise the question on the role of cyclin D1 at early stages of hepatocarcinogenesis in the Mdr2-KO HCC model. Furthermore, we show that most liver tumors in Mdr2-KO mice were characterized by the absence of b-catenin activation. In conclusion, the Mdr2-KO mouse may serve as a model for b-catenin-negative subgroup of human HCCs characterized by low nuclear cyclin D1 levels in tumor cells and by down-regulation of multiple tumor suppressor genes.
Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice.
Age
View SamplesWe studied the molecular mechanisms of hepatocellular carcinoma (HCC) initiation and promotion using the Mdr2-knockout (Mdr2-KO) mice at pre-cancerous stages of liver disease. These mice lack the liver-specific P-glycoprotein responsible for phosphatidylcholine transport across the canalicular membrane. Portal inflammation ensues at an early age followed by the development of HCC between the ages of 12 and 15 months. Liver tissue samples of Mdr2-KO and control Mdr2-heterozygotes mice aged 3 and 12 months, were subjected to histological, biochemical and gene expression profiling analysis using Affymetrix Mouse Genome Array.
Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice.
Age
View SamplesBacteria are known to respond to various environmental stimuli including nutrient deprivation, osmotic stress, and exposure to antibiotics. Our experimental data showed that P. aeruginosa biofilm formed in urinary catheters is very suseptible to gentamicin treatment when combined with exposure to surface acoustic waves
No associated publication
No sample metadata fields
View SamplesThe purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesGene expression profile comparison from fibroblasts of Huntington individuals and normal ones
Gene expression profile in fibroblasts of Huntington's disease patients and controls.
Sex, Age, Specimen part, Disease
View SamplesComparison of the differential expression mRNA profiles from the brain cortex of hypoxia and normaixa rats by silica microarray chip
No associated publication
Specimen part
View SamplesBone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats
Identification of genes influencing skeletal phenotypes in congenic P/NP rats.
No sample metadata fields
View SamplesFemoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats
Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.
No sample metadata fields
View SamplesGene expression was measured using microarrays in 8 hour postfertilization embryos, comparing control versus ethanol-treated (2 to 8 hours postfertilization) embryos. This experiment was performed to determine the gene expression changes that occur in response to ethanol treatment as a model of fetal alcohol spectrum disorder.
Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects.
Age, Specimen part, Treatment
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