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

Abstract

The ®broblast 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 signi®cantly regulated through the AP-1 or E-box sites in the promoter. These results illustrate di erences between the mechanism of induction in response to serum and EGF. Oncogene (2001) 20, 1730 ± 1738.

Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1

“…First, both KLF5 and FGF-BP were reported to be induced by TPA (Harris et al, 1998;Sun et al, 2001;Sur et al, 2002) and the MAPK pathway (Harris et al, 2001;Sun et al, 2001;Chanchevalap et al, 2006). In addition, microarray studies suggest that FGF-BP is a downstream gene of KLF5 in vitro and in vivo (Chen et al, 2006;Wan et al, 2008).…”

“…To test this, we manually analysed the FGF-BP proximal promoter (Harris et al, 1998(Harris et al, , 2001Kagan et al, 2003) and found two potential KLF5 binding sites (Figure 4a). Then, we generated two luciferase reporter constructs by cloning the FGF-BP promoter (À217/ þ 61 and À128/ þ 61) into the PGL3-BASIC plasmid.…”

Fibroblast Growth Factors and their Emerging Cancer-Related Aspects

“…When bound to FGF-2, FGF-BP reduces the availability of bFGF to heparin sulfate molecules, stimulating the growth of prostate and adrenal cancer cells in an FGF-2 dependent manner [166,167]. Reduction in the levels of FGF-BP has been correlated with the inhibition of angiogenic activity within the xenograft models of squamous cell cancer, colon cancer as well as prostate cancer [168,169].…”

The human papillomavirus (HPV) 16 E6 oncoprotein leads to an increase in gene expression of the angiogenic switch molecule FGF-BP in non-immortalized human keratinocytes

“…Additionally, a negative regulatory non-canonical E-box element was found, which represses FGF-BP promoter activity through binding of a protein complex in which USF, c-myc and Max proteins might be involved, as demonstrated by in vivo gel shift analysis (Harris et al, 2000b). Recently it has been shown that the serum-dependent induction of FGF-BP transcription is mediated through activation of protein kinase C, leading to the activation of ERK and p38 MAP kinase (Harris et al, 2001). The C/EBP element of the FGF-BP promoter is required for the serum response of this promoter (Harris et al, 2001).…”

“…Recently it has been shown that the serum-dependent induction of FGF-BP transcription is mediated through activation of protein kinase C, leading to the activation of ERK and p38 MAP kinase (Harris et al, 2001). The C/EBP element of the FGF-BP promoter is required for the serum response of this promoter (Harris et al, 2001).…”