Serum induction of the fibroblast growth factor-binding protein (FGF-BP) is mediated through ERK and p38 MAP kinase activation and C/EBP-regulated transcription

Oncogene. 2001 Mar 29;20(14):1730-8. doi: 10.1038/sj.onc.1204249.


The fibroblast growth factor-binding protein (FGF-BP) modulates FGF activity through binding and release from the extracellular matrix. Consequently, the expression of FGF-BP in certain tumor types is a rate-limiting regulator of FGF-mediated angiogenesis. FGF-BP is upregulated in squamous cell carcinoma by treatment with mitogens such as EGF or TPA. In this study, we investigated the regulation of FGF-BP gene expression by serum. Treatment of serum-starved ME-180 cells with fetal bovine serum (FBS) resulted in a rapid increase in steady-state levels of FGF-BP mRNA and in the rate of FGF-BP gene transcription. Serum induction of FGF-BP mRNA was not mediated through EGF receptor activation but was dependent on PKC, as well as ERK kinase (MEK) and p38 MAP kinase activation. Promoter analysis showed that C/EBP is the main promoter element required for the serum response. Unlike EGF-activation of FGF-BP, transcriptional induction by serum is not significantly regulated through the AP-1 or E-box sites in the promoter. These results illustrate differences between the mechanism of induction in response to serum and EGF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blood Physiological Phenomena*
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cells, Cultured
  • Endopeptidases / genetics*
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / physiology
  • Gene Expression Regulation
  • Humans
  • Mitogen-Activated Protein Kinases / physiology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Promoter Regions, Genetic
  • Protein Kinase C / physiology
  • Transcription Factor AP-1 / physiology
  • Transcription, Genetic*
  • p38 Mitogen-Activated Protein Kinases


  • CCAAT-Enhancer-Binding Proteins
  • Transcription Factor AP-1
  • Epidermal Growth Factor
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Endopeptidases