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



: Jaakkola P, Maatta A, Jalkanen M

Publisher: STOCKTON PRESS

: 1998

Oncogene

ONCOGENE

: ONCOGENE

: 17

: 10

: 1279

: 1286

: 8

: 0950-9232

DOI: https://doi.org/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 vel sn. 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-ls 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.

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