Adenovirus-Mediated Transfer of a Truncated Fibroblast Growth Factor (FGF) Type I Receptor Blocks FGF-2 Signaling in Multiple Pancreatic Cancer Cell Lines

Jörg Kleeff, Nayantara H. Kothari, Helmut Friess, Hung Fan, Murray Korc

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Pancreatic ductal adenocarcinomas (PDACs) overexpress several members of the fibroblast growth factor (FGF) family of ligands and the type I FGF receptor (FGFR-1), and enhanced FGF-2 protein levels correlate with shorter postoperative survival of patients with PDAC. In this study, we investigated the effects of FGF-2 on cell proliferation and mitogen-activated protein kinase (MAPK) activation before and after abrogation of FGFR-1-dependent signaling in 4 pancreatic cancer cell lines (ASPC-1, COLO-357, MIA-PaCa-2, and PANC-1). Signaling was blocked by infecting the cells with an adenoviral vector encoding for a truncated FGFR-1 (AdtrFGFR-1). FGF-2 enhanced the growth of all 4 cell lines and activated MAPK in 3 of these cell lines. Infection with the AdtrFGFR-1 virus resulted in abundant expression of the truncated FGFR-1 at the RNA and protein level, markedly attenuated FGF-2-induced proliferation in all 4 tested cell lines, and decreased FGF-2-dependent MAPK activation in the 3 cell lines in which FGF-2 activated this pathway. These findings suggest that FGFR-1-mediated mitogenesis in multiple pancreatic cancer cells can be efficiently blocked with an adenoviral vector encoding a truncated FGFR-1, raising the possibility that AdtrFGFR-1 may ultimately have a therapeutic role in PDAC.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalPancreas
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2004

Keywords

  • Adenoviral vector
  • Fibroblast growth factor receptor
  • Fibroblast growth factor signaling
  • Pancreatic cancer

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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