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

Fingerprint

Hepatocellular Carcinoma
Chromosomes
Methylation
Genes
Loss of Heterozygosity
Electrophoresis
Exons
Signal Transduction
Carrier Proteins
Alleles
Genome
Cytokines
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Combined hypermethylation and chromosome loss associated with inactivation of SSI-1/SOCS-1/JAB gene in human hepatocellular carcinomas. / Nagai, Hisaki; Kim, Yong Sung; Konishi, Noboru; Baba, Masaru; Kubota, Takeo; Yoshimura, Akihiko; Emi, Mitsuru.

In: Cancer Letters, Vol. 186, No. 1, 01.12.2002, p. 59-65.

Research output: Contribution to journalArticle

Nagai, Hisaki ; Kim, Yong Sung ; Konishi, Noboru ; Baba, Masaru ; Kubota, Takeo ; Yoshimura, Akihiko ; Emi, Mitsuru. / Combined hypermethylation and chromosome loss associated with inactivation of SSI-1/SOCS-1/JAB gene in human hepatocellular carcinomas. In: Cancer Letters. 2002 ; Vol. 186, No. 1. pp. 59-65.
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