Effect of v-erbA on T3-responsive genes in AML-12 hepatocytes. Mus musculus

The v-erbA oncogene belongs to a superfamily of transcription factors called nuclear receptors, which includes the thyroid hormone receptors (TRs) responsible for mediating the effects of thyroid hormone (T3). Nuclear receptors bind to specific DNA sequences in the promoter region of target genes and v-erbA is known to exert a dominant negative effect on the activity of the TRs. The repressor activity of v-erbA has been linked to the development of hepatocellular carcinoma (HCC) in a mouse model. We have used microarray analysis to identify genes differentially expressed in hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to T3. We have found that v-erbA can negatively regulate expression of T3-responsive genes known to have a protective function against tumor development. We have also identified a number of v-erbA- (but not T3-) responsive genes that are known to be involved in carcinogenesis and which may play a role in the development of HCC. Overall design: AML12 control cells and v-erbA-transfected AML12 cells were exposed to 10 nM T3 for 3h or 24h. Using microarray analysis, we compared gene expression in the presence and absence of v-erbA and identified T3-regulated genes differentially expressed in the presence of v-erbA.