Inactivation of SSI-1, a JAK/STAT inhibitor, in human hepatocellular carcinomas, as revealed by two-dimensional electrophoresis

Background/Aims: Hepatocellular carcinoma (HCC) is one of the most common human cancers, and many efforts have been paid to discover aberrant expression control in HCC, however the specific molecular mechanisms involved in hepatocarcinogenesis remain to be determined. Methods: To investigate genomic changes that occur in human primary hepatocellular carcinomas (HCC), we carried out restriction landmark genomic scanning. This two-dimensional electrophoretic system displays 2000–3000 NotI-landmark sites in a single gel. Results: We detected one landmark spot that showed diminished signal intensities in a majority of the HCCs we examined. Cloning revealed that this spot represented a NotI-cluster sequence that was enriched with CpG dinucleotides in the promoter region of a gene encoding Janus kinase (JAK)-binding protein, SSI-1 (also known as JAB1 or SOCS-1). Expression of the SSI-1 gene was markedly reduced in half of eight HCCs analyzed. Conclusions: This protein regulates the Janus kinase signal transducers and activators of transcription signal transduction pathway, which transmits signals from cytokines to the intracellular apparatus. These data suggest that dysregulation of the pathway relate with progression of HCC.