The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner

Oncogene. 1998 Sep 10;17(10):1279-86. doi: 10.1038/sj.onc.1202002.


The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both in keratinocytes and in fibroblasts during development and tissue regeneration. Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF but not by FGF-2. In fibroblasts it was stimulated by FGF-2 but not by EGF. Likewise, the recently discovered FGF-inducible response element (FiRE) on the gene of syndecan-1 was stimulated by FGF-2 in fibroblasts and by EGF in keratinocytes, but not vice versa. The FiRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1). The growth factor-stimulated binding of these transcription factors, as well as their requirement for FiRE activation, varied between the two cell types. First, although AP-1s were required for activation of FiRE in both cell types, the binding of AP-1 to FiRE was increased by growth factor-stimulation only in fibroblasts and not in keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE in fibroblasts. Thirdly, EGF, which did not activate FiRE in fibroblasts, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FiRE in keratinocytes was not needed in fibroblasts. These data suggest mechanisms by which members of the EGF- and FGF-families can differentially stimulate transcription through AP-1 regulated elements in a cell type-specific manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / drug effects*
  • 3T3 Cells / metabolism
  • Animals
  • Binding Sites
  • DNA-Binding Proteins*
  • Epidermal Growth Factor / pharmacology*
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors*
  • Gene Expression Regulation / drug effects
  • Growth Substances / pharmacology
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Nuclear Proteins / metabolism
  • Proteins / drug effects
  • Proteins / metabolism
  • Proteoglycans / drug effects
  • Proteoglycans / genetics
  • Proteoglycans / metabolism
  • Response Elements / drug effects*
  • Syndecan-1
  • Syndecans
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism
  • Upstream Stimulatory Factors


  • DNA-Binding Proteins
  • Emr4 protein, mouse
  • Fgf7 protein, mouse
  • Fibroblast Growth Factor 10
  • Growth Substances
  • Membrane Glycoproteins
  • Nuclear Proteins
  • Proteins
  • Proteoglycans
  • Sdc1 protein, mouse
  • Syndecan-1
  • Syndecans
  • Transcription Factor AP-1
  • Transcription Factors
  • Upstream Stimulatory Factors
  • Usf1 protein, mouse
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Epidermal Growth Factor