Differential regulation of albumin gene expression by heparin-binding epidermal growth factor-like growth factor in alpha-fetoprotein-producing and -nonproducing human hepatoma cells

Tumour Biol. 1999 May-Jun;20(3):130-8. doi: 10.1159/000030055.

Abstract

The effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on albumin gene expression were analyzed in alpha-fetoprotein (AFP)-producing and AFP-nonproducing human hepatoma cells, HuH-7 and huH-1/cl.2, in which the AFP silencer is inactive and active, respectively. HB-EGF selectively suppressed the AFP enhancer activity, resulting in decreased levels of both albumin and AFP mRNA in HuH-7 cells. In contrast, HB-EGF did not influence the albumin transcripts in huH-1/cl.2 cells or primary culture of rat hepatocytes, although the AFP enhancer activity was reduced by HB-EGF in huH-1/cl.2 cells as well as in HuH-7 cells. These results indicate that the AFP silencer interacts with the AFP enhancer to block its activity regulating both the albumin and AFP promoters, and that HB-EGF downregulates the albumin gene expression only in the absence of the AFP silencer through the repression of the AFP enhancer activity.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Division / drug effects
  • Enhancer Elements, Genetic
  • Epidermal Growth Factor / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Liver / drug effects
  • Liver / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Promoter Regions, Genetic
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / pharmacology
  • Serum Albumin / biosynthesis
  • Serum Albumin / genetics*
  • Transfection
  • Tumor Cells, Cultured
  • alpha-Fetoproteins / biosynthesis*
  • alpha-Fetoproteins / genetics

Substances

  • HBEGF protein, human
  • Hbegf protein, rat
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • Serum Albumin
  • alpha-Fetoproteins
  • Epidermal Growth Factor