title: Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo.
abstract: OBJECTIVE
  Fibroblast growth factors (FGFs) are mitogenic polypeptides that activate specific cell surface FGF receptors (FGFRs). Pancreatic cancers overexpress basic FGF (bFGF) and the type I FGF receptor (FGFR-1), and overexpression of bFGF has been correlated with decreased patient survival. The aim of this study was to examine the effects of abrogation of FGFR-1-dependent signaling on pancreatic cancer cell growth.
  
  
  METHODS
  PANC-1 human pancreatic cancer cells were transfected with a truncated FGFR-1 complementary DNA (FGFR405), resulting in the expression of a kinase-deficient receptor. Activation of endogenous FGFR-1 was assessed in immunoblot studies with antiphosphotyrosine and anti-active mitogen-activated protein (MAP) kinase antibodies. Effects on cell growth were determined in vitro and in nude mice.
  
  
  RESULTS
  PANC-1 clones expressing the truncated receptor showed attenuated receptor tyrosine phosphorylation and MAP kinase activation in response to bFGF, decreased basal cell growth, and a marked decrease in tumor-forming potential in vivo. Confirmatory experiments with MIA PaCa-2 pancreatic cancer cells indicated that FGFR405 also attenuated FGF-dependent MAP kinase activation in this cell line.
  
  
  CONCLUSIONS
  The findings suggest that FGFR-dependent signaling is crucial for pancreatic cancer growth and raise the possibility that inhibition of FGFR signaling may ultimately prove useful as a therapeutic option in patients with pancreatic cancer.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University of California, Irvine, California 92697, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wagner
authors.forename: M E
authors.initials: ME
authors.lastname: Lopez
authors.forename: M
authors.initials: M
authors.lastname: Cahn
authors.forename: M
authors.initials: M
authors.lastname: Korc
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000628:therapy; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases