Reduced Expression of Insulin-Like Growth Factor Binding protein-3 and Its Promoter Hypermethylation in Human Hepatocellular Carcinoma

Cancer Lett. 2002 Feb 25;176(2):149-58. doi: 10.1016/s0304-3835(01)00736-4.

Abstract

Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Reduced expression of the IGFBP-3 was observed in nine out of 12 human hepatocellular carcinomas (HCC) (75%). Promoter hypermethylation of the IGFBP-3 was detected in four out of 12 HCCs (33%) although mutations were not identified. The expression of IGFBP-3 was restored by the demethylating agent 5-aza-2'-deoxycytidine in HCC cell line with promoter hypermethylation (HepG2). As IGFBP-3 functions like a tumor suppressor gene, it may be used as a therapeutic target for HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Base Sequence
  • Blotting, Northern
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Chromosomes, Human, Pair 7
  • DNA Methylation*
  • DNA, Complementary / metabolism
  • Decitabine
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / biosynthesis*
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Loss of Heterozygosity
  • Mannosephosphates / metabolism
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic*
  • RNA / metabolism
  • Receptor, IGF Type 2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Antimetabolites, Antineoplastic
  • DNA, Complementary
  • Insulin-Like Growth Factor Binding Protein 3
  • Mannosephosphates
  • Receptor, IGF Type 2
  • mannose-6-phosphate
  • RNA
  • Decitabine
  • Azacitidine