Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo

M. Wagner, M. E. Lopez, M. Cahn, Murray Korc

Research output: Contribution to journalArticle

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Abstract

Background and Aims: 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 antiactive 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.

Original languageEnglish (US)
Pages (from-to)798-807
Number of pages10
JournalGastroenterology
Volume114
Issue number4 I
DOIs
StatePublished - 1998
Externally publishedYes

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Fibroblast Growth Factor Receptors
Pancreatic Neoplasms
Fibroblast Growth Factor 1
Growth
Mitogen-Activated Protein Kinases
Fibroblast Growth Factors
In Vitro Techniques
Fibroblast Growth Factor 2
Nude Mice
Phosphotransferases
Complementary DNA
Clone Cells
Phosphorylation
Cell Line
Peptides
Survival
Antibodies

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo. / Wagner, M.; Lopez, M. E.; Cahn, M.; Korc, Murray.

In: Gastroenterology, Vol. 114, No. 4 I, 1998, p. 798-807.

Research output: Contribution to journalArticle

Wagner, M. ; Lopez, M. E. ; Cahn, M. ; Korc, Murray. / Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo. In: Gastroenterology. 1998 ; Vol. 114, No. 4 I. pp. 798-807.
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