GSE119806 Promyelocytic Leukemia Protein Deficiency Leads to Spontaneous Formation of Liver Tumors in HCV Transgenic Mice

Contributors : K Straub ; P Kocabayoglu ; H A Baba ; M Trippler ; H Wedemeyer ; K HerzerSeries Type : Expression profiling by arrayOrganism : Mus musculusPersistent infection with hepatitis C virus (HCV) is a known risk factor for the development of hepatocellular carcinoma (HCC). The lack of the tumor suppressor promyelocytic leukemia protein (PML) in combination with HCV fosters hepatocarcinogenesis via induction of HCC using diethylnitrosamine (DEN) in a rodent model. However, the spontaneous development of malignant lesions in PML-deficient mice with an HCV-transgene (HCVtg) has not been investigated thus far. We crossed PML-deficient mice with HCV transgene expressing mice and observed the animals for a period of 12 months. Livers were examined macroscopically and histologically. Gene expression analysis was performed on these samples, and compared with expression of selected genes in human samples of patients undergoing liver transplantation for HCC. In vitro studies were performed in order to analyze the selected pathways. Genetic depletion of PML in combination with HCVtg coincided with an increased hepatocyte proliferation, resulting in development of HCCs in 40% of the PML-deficient livers. No tumor development was observed in mice with either the PML-knockout (PML-/-) or HCVtg alone. Gene expression profiling uncovered pathways involved in cell proliferation, such as NLRP12 and RASFF6. These findings were verified in samples from human livers of patients un...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research