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 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 significantly regulated through the AP-1 or E-box sites in the promoter. These results illustrate differences between the mechanism of induction in response to serum and EGF.
Harris
V K
VK
Department of Oncology, Vincent T. Lombardi Cancer Center, Georgetown University, Washington DC 20007, USA.
Kagan
B L
BL
Ray
R
R
Coticchia
C M
CM
Liaudet-Coopman
E D
ED
Wellstein
A
A
Tate Riegel
A
A
D001790:Blood Physiological Phenomena; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002478:Cells, Cultured; D010450:Endopeptidases / Q000235:genetics*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases
D022762:CCAAT-Enhancer-Binding Proteins; D018808:Transcription Factor AP-1; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010450:Endopeptidases