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

The fibroblast growth factor-binding protein (FGF-BP) modulates FGF activit y through binding and release from the extracellular matrix, Consequently, the expression of FGF-BP in certain tumor types is a rate-limiting regulato r of FGF-mediated angiogenesis. FGF-BP is upregulated in squamous cell carc inoma by treatment with mitogens such as EGF or TPA, In this study, we inve stigated the regulation of FGF-BP gene expression by serum. Treatment of se rum-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 ge ne transcription. Serum induction of FGF-BP mRNA was not mediated through E GF 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-activati on of FGF-BP, transcriptional induction by serum is not significantly regul ated through the AP-I or E-box sites in the promoter. These results illustr ate differences between the mechanism of induction in response to serum and EGF.