Interferon-alpha-induced inhibition of B16 melanoma cell proliferation: interference with the bFGF autocrine growth circuit

Biochem Biophys Res Commun. 1999 Sep 7;262(3):838-44. doi: 10.1006/bbrc.1999.1292.


The molecular mechanisms underlying the growth inhibition induced by interferon-alpha (IFN-alpha) in B16 murine melanoma cells were investigated. IFN-alpha did not induce cell apoptosis, but strongly interfered with the synthesis of basic fibroblast growth factor (bFGF), which acts as an autocrine growth factor in this system. Inhibition of bFGF synthesis was observed at the same concentrations (50-500 pM, 10-100 U/ml) of IFN-alpha able to induce growth arrest of B16 melanoma cells. Although the synthesis of acidic (a)FGF was only slightly affected by IFN-alpha, the cytokine induced release of an aFGF-related low-molecular-weight peptide, which was able to interfere with bFGF binding to surface receptors. Thus, the molecular mechanisms of IFN-alpha activity on melanoma cells include a specific modulation of the bFGF autocrine circuit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects*
  • Cysteine / metabolism
  • Fibroblast Growth Factor 1 / physiology
  • Fibroblast Growth Factor 2 / biosynthesis
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / physiology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-alpha / pharmacology*
  • Kinetics
  • Melanoma, Experimental
  • Methionine / metabolism
  • Mice
  • RNA, Messenger / genetics
  • Recombinant Proteins / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • Interferon-alpha
  • RNA, Messenger
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Methionine
  • Cysteine