Expression of the IIIc variant of FGF receptor-1 confers mitogenic responsiveness to heparin and FGF-5 in TAKA-1 pancreatic ductal cells

Marko Kornmann, Martha E. Lopez, Hans G. Beger, Murray Korc

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background. Fibroblast growth factors (FGFs) contribute to angiogenesis and mitogenesis by binding to tyrosine kinase receptors termed FGF receptors (FGFRs). FGF-5 is a secreted FGF that is believed to preferentially act via the IIIc splice variant of FGFR-1. Human pancreatic ductal carcinoma cells express FGF-5 and FGFR-1 IIIc, implying a potential for autocrine growth modulation. Aim. In this study we investigated the importance of FGFR-1 IIIc expression for FGF-5 mitogenic signaling in a pancreatic ductal cell line. Methods. A cDNA encoding FGFR-1 IIIc was expressed in the well-differentiated TAKA-1 Syrian hamster pancreatic ductal cell line. Results. TAKA-1 cells secrete FGF-5, but were found not to express FGFR-1 and to be unresponsive to exogenous FGF-5. In contrast, TAKA-1 clones expressing FGFR-1 IIIc were growth stimulated in the presence of FGF-5 and displayed enhanced mitogen-activated protein kinase (MAPK) activity in the presence of FGF-5. PD98059, an inhibitor of this pathway, inhibited FGF-5-induced growth in these clones. Conclusion. Our data demonstrate that FGFR-1 IIIc can mediate FGF-5-induced mitogenesis via the MAPK pathway in pancreatic ductal cells, and suggest that expression of FGFR-1 IIIc in conjunction with FGF-5 may contribute to the pathobiology of human pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalInternational Journal of Pancreatology
Volume29
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • Fibroblast growth factor
  • Fibroblast growth factor receptor
  • Mitogen-activated protein kinase
  • Mitogenic signaling
  • Pancreatic cancer
  • Pancreatic ductal cells

ASJC Scopus subject areas

  • Oncology
  • Endocrinology
  • Gastroenterology

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