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

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Summary

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.

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Authors and Affiliations

  1. Departments of Medicine, Biological Chemistry and Pharmacology, University of California, Irvine, Med. Sci. I C240, 92697, Irvine, CA, U.S.A.

    Martha E. Lopez & Murray Korc

  2. Department of General Surgery, University of Ulm, 89070, Ulm, Germany

    Marko Kornmann & Hans G. Beger

Authors
  1. Marko Kornmann
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  2. Martha E. Lopez
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  3. Hans G. Beger
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  4. Murray Korc
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Correspondence to Murray Korc.

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Kornmann, M., Lopez, M.E., Beger, H.G. et al. Expression of the IIIc variant of FGF receptor-1 confers mitogenic responsiveness to heparin and FGF-5 in TAKA-1 pancreatic ductal cells. International Journal of Pancreatology 29, 85–92 (2001). https://doi.org/10.1385/IJGC:29:2:085

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  • DOI: https://doi.org/10.1385/IJGC:29:2:085

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