Expression of the IIIc variant of FGF receptor-1 confers mitogenic responsiveness to heparin and FGF-5 in TAKA-1 pancreatic ductal cells.
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-1IIIc, implying a potential for autocrine growth modulation.


OBJECTIVE
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.


CONCLUSIONS
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.
Kornmann
M
M
Department of Medicine, University of California, Irvine 92697, USA. mkorc@uci.edu
Lopez
M E
ME
Beger
H G
HG
Korc
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010183:Pancreatic Ducts / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000502:physiology*
D017468:Receptors, Fibroblast Growth Factor; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors; D006493:Heparin; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases