Hypermethylation-associated inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human pancreatic cancers.

SOCS-1, a JAK-binding protein (SSI-1/SOCS-1/JAB), regulates the JAK/STAT signal transduction pathway that relays signals from various cytokines in the extracellular matrix into the cell. Inactivation of the SOCS-1 gene by methylation has been previously described in hepatocellular carcinomas and multiple myeloma. The purpose of the present work was to analyze the expression of the SOCS-1 gene and identify inactivation of this gene by methylation in pancreatic cancers. 20 samples were analyzed. We identified the expression of SOCS-1 gene using RT-PCR and the mechanism of inactivation in this gene by methylation assay. We documented marked suppression of SOCS-1 mRNA and reduction of SOCS-1 protein in 7 of 14 primary pancreatic cancers examined; moreover, CpG-rich regions upstream of the SOCS-1 gene were hypermethylated in 8 of the 14 tumors. The results suggested that this gene is silenced in a substantial portion of pancreatic cancers through mechanisms that cause methylation in the promoter region.