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

Hisaki Nagai, Yong Sung Kim, Noboru Konishi, Masaru Baba, Takeo Kubota, Akihiko Yoshimura, Mitsuru Emi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalCancer Letters
Volume186
Issue number1
DOIs
Publication statusPublished - 2002 Dec 1
Externally publishedYes

Keywords

  • Hepatocellular carcinoma (HCC)
  • Methylation
  • SSI-1/SOCS-1/JAB

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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