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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 volume 20, pages 1730–1738 (2001)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by a Susan G. Komen Foundation award, National Institute of Health and National Cancer Institute grant CA71508, and an American Cancer Society grant CB202.

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Author notes

  1. Emmanuelle D Liaudet-Coopman

    Present address: INSERM, Universite de Montpellier 1, Montpellier, France

  2. Violaine K Harris and Benjamin L Kagan: VK Harris and BL Kagan contributed equally to this work

Authors and Affiliations

  1. Department of Oncology, Vincent T. Lombardi Cancer Center, Georgetown University, Washington, 20007, DC, USA

    Violaine K Harris, Ranjan Ray, Christine M Coticchia, Emmanuelle D Liaudet-Coopman, Anton Wellstein & Anna Tate Riegel

  2. Department of Pharmacology, Georgetown University, Washington, 20007, DC, USA

    Benjamin L Kagan

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  1. Violaine K Harris
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Harris, V., Kagan, B., Ray, R. 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, 1730–1738 (2001). https://doi.org/10.1038/sj.onc.1204249

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