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Transcription profiling of MDR2 knockout mice vs heterozygotes sampled at multiple time points in the early stages of liver carcinogenesis to identify the molecular mechanisms of HCC initiation and promotion


ABSTRACT: We 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. The RNA samples from Mdr2-KO and control heterozygous mice aged 3 and 12M (3 males in each experimental group) were subjected to genome scale gene expression profiling with Affymetrix Mouse Array. The gene expression values were extracted with the help of MAS 5.0 software, and analyzed by cluster analysis, and by fold change filtering

ORGANISM(S): Mus musculus

SUBMITTER: Mark Katzenellenbogen 

PROVIDER: E-GEOD-4612 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice.

Katzenellenbogen Mark M   Pappo Orit O   Barash Hila H   Klopstock Naama N   Mizrahi Lina L   Olam Devorah D   Jacob-Hirsch Jasmine J   Amariglio Ninette N   Rechavi Gidi G   Mitchell Leslie Ann LA   Kohen Ron R   Domany Eytan E   Galun Eithan E   Goldenberg Daniel D  

Cancer research 20060401 8


Molecular events preceding the development of hepatocellular carcinoma were studied in the Mdr2-knockout (Mdr2-KO) mice. 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 hepatocellular carcinoma development after the age of 1 year. Liver tissue samples of Mdr2-KO mice in the early and late precancerous stages of liver disease were subjected to histologic, biochem  ...[more]

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