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
Vk. Harris et al., 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, 20(14), 2001, pp. 1730-1738
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.