Expressions of epidermal growth factor family and its receptor in hepatocellular carcinoma cell lines: relationship to cell proliferation

Int J Oncol. 1999 Mar;14(3):453-60. doi: 10.3892/ijo.14.3.453.


In 6 HCC cell lines, clear expressions of EGFR and TGF-alpha were found in flow cytometry, while expressions of EGF, HB-EGF and AR were quite low. TGF-alpha secretion into culture supernatants became measurable when TPA 0.5 microM was added. TPA accelerated the proliferation of KYN-3 cells, and anti-TGF-alpha neutralizing antibody suppressed this proliferation in a dose-dependent manner. Addition of exogenous TGF-alpha, EGF, AR, or HB-EGF with heparin accelerated cell proliferation. In non-stimulated cultures, cell proliferation was suppressed by anti-EGFR neutralizing antibody, but not by the antibodies for EGF, TGF-alpha, AR and HB-EGF. HCC may possess a paracrine system regulated by these 4 ligands, and an autocrine system, under a certain condition, via TGF-alpha and EGFR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphiregulin
  • Antibodies / immunology
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Division
  • Cell Line
  • Culture Media / chemistry
  • EGF Family of Proteins
  • Epidermal Growth Factor / biosynthesis*
  • Epidermal Growth Factor / immunology
  • Epidermal Growth Factor / physiology
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / physiology
  • Glycoproteins / biosynthesis
  • Glycoproteins / physiology
  • Growth Substances / biosynthesis
  • Growth Substances / physiology
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Ligands
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Transforming Growth Factor alpha / biosynthesis*
  • Transforming Growth Factor alpha / immunology
  • Transforming Growth Factor alpha / physiology


  • AREG protein, human
  • Amphiregulin
  • Antibodies
  • Culture Media
  • EGF Family of Proteins
  • Glycoproteins
  • Growth Substances
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor
  • ErbB Receptors