NFkB dependent gene expression in a Mdr2-KO hepatocellular carcinoma (HCC) mouse model using a IkB-Superrepressor. Mus musculus

This study aims on the identification of the NF-kB dependent gene regulatory network during inflammation-associated liver carcinogenesis using the well-established Mdr2 knockout mouse model. We could identify 367 differentially expressed genes comparing expression profiles of tumor samples from Mdr2-KO mice to tumor samples derived from mice with an additional hepatocyte specific expression of an IkB-superrepressor. This IkB-superrepresser is undegradable upon ubiquitinylation initialized by Ikk dependent phosphorylation and therefore impedes NFkB activity. Keywords: NFkB, IkB-superrepressor, inflammation-associated liver carcinogenesis, Mdr2-KO mouse model, hepatocellular carcinoma, gene expression, microarray Overall design: In the experiments shown here, we compare gene expression profiles of HCCs from 4 idividual mice harboring a biallelic Mdr2 knockout to HCC specimen of 6 individual mice with Mdr2 knockout and a hepatocyte specific expression of the IkB-superrepressor. Each individual sample was hybridized aginst a universal reference mouse pool (Stratagene) on a two-color microarray. Furthermore was each sample/reference hybridization conducted as a dye swap experiment yielding two technical replicates with inverted dye channel orientation per sample. In addition a biological control using wildtype liver tissue from mice of the same genetic background was hybridized the same way aginst a universal reference. The latter was used to build a sample/control ratio for displays of indirect comparison.