Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1

Cancer Res. 2003 Jun 15;63(12):3043-8.

Abstract

Through a genome-wide cDNA microarray, we identified that the paternally expressed gene 10 (PEG10) was highly expressed in a great majority of hepatocellular carcinomas, although its expression was absent in normal liver cells. Exogenous expression of PEG10 conferred oncogenic activity and transfection of hepatoma cells with antisense S-oligonucleotides suppressing PEG10 resulted in their growth inhibition. Additional experiments revealed that PEG10 protein associated with SIAH1, a mediator of apoptosis, and that overexpression of PEG10 decreased the cell death mediated by SIAH1. These findings suggested that development of drug(s) inhibiting PEG10 activity could be a novel approach for the treatment of hepatocellular carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Division
  • Cell Line
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / metabolism
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Protein Interaction Mapping
  • Proteins / antagonists & inhibitors
  • Proteins / genetics
  • Proteins / physiology*
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins / physiology
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Ubiquitin-Protein Ligases

Substances

  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oligodeoxyribonucleotides, Antisense
  • PEG10 protein, human
  • Proteins
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins