The Serum Reponse Factor (SRF) is involved in the transcriptional upregulation of the functional p53 inhibitor MDM 4 in hepatocellular carcinoma

MDM 4 is a p53 binding protein that negatively regulates p53-dependent transcription. MDM 4 was found overexpressed in a variety of human cancers and amplifications of the MDM 4 gene locus were reported most of these tumor entities. We have previously demonstrated that MDM 4 is upregulated in about 50% of human hepatocellular carcinomas (HCC), both at messenger RNA (mRNA) and protein level. Although we identified 1q32 gains as a mechanism leading to MDM 4 overexpression in human HCC, many liver tumors display a balanced MDM 4 gene locus. Thus, additional mechanisms are responsible for aberrant MDM 4 expression i…