Combined hypermethylation and chromosome loss associated with inactivation of SSI-1/SOCS-1/JAB gene in human hepatocellular carcinomas

Cancer Lett. 2002 Dec 1;186(1):59-65. doi: 10.1016/s0304-3835(02)00244-6.


We previously demonstrated using restriction landmark genomic scanning-based 2-dimensional genome electrophoresis method decreased results of 16 primary hepatocellular carcinomas (HCCs) revealed reduction of intensity of 60 NotI-landmark spots, and increase in five spots that were frequently observed in HCCs. Most frequently decreased spot (14/16 HCCs) was identified to it corresponds to a gene encoding SSI-1, a JAK-binding protein (SSI-1/SOCS-1/JAB) that regulated the JAK/STAT signal transduction pathway. This signaling pathway is important for relaying signals from various cytokines outside the cell to the inside. Expression level of SOCS-1 messenger RNA was markedly suppressed in 50% of HCCs (4/8). Loss of heterozygosity at the SSI-1 gene, was found in all cases with aberrant expression. Methylation analysis of the CpG-rich regions of SSI-1 gene revealed hypermethylation of these regions. In an additional series of methylation analysis using 30 HCCs, 16 (53%) showed hypermethylation of the gene. These results indicate that the SSI-1 gene is silenced in a substantial portion of HCC though the combined mechanisms of methylation of either 5' or exon CpG rich regions and by a chromosomal loss of the remaining allele.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carrier Proteins / genetics*
  • DNA Methylation*
  • DNA-Binding Proteins / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Liver Neoplasms / genetics*
  • Loss of Heterozygosity*
  • Repressor Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators / physiology


  • Carrier Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Repressor Proteins
  • SOCS1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators