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 Citations (Scopus)

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 2004
Externally publishedYes

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Receptor, Fibroblast Growth Factor, Type 2
Fibroblast Growth Factors
Fibroblast Growth Factor 2
Pancreatic Neoplasms
Adenoviridae
Cell Line
Adenocarcinoma
Mitogen-Activated Protein Kinases
Receptor, Fibroblast Growth Factor, Type 1
Mitogen-Activated Protein Kinase 3
Proteins
Cell Proliferation
RNA
Ligands
Viruses
Survival
Growth
Infection

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

Adenovirus-Mediated Transfer of a Truncated Fibroblast Growth Factor (FGF) Type I Receptor Blocks FGF-2 Signaling in Multiple Pancreatic Cancer Cell Lines. / Kleeff, Jörg; Kothari, Nayantara H.; Friess, Helmut; Fan, Hung; Korc, Murray.

In: Pancreas, Vol. 28, No. 1, 01.2004, p. 25-30.

Research output: Contribution to journalArticle

Kleeff, Jörg ; Kothari, Nayantara H. ; Friess, Helmut ; Fan, Hung ; Korc, Murray. / Adenovirus-Mediated Transfer of a Truncated Fibroblast Growth Factor (FGF) Type I Receptor Blocks FGF-2 Signaling in Multiple Pancreatic Cancer Cell Lines. In: Pancreas. 2004 ; Vol. 28, No. 1. pp. 25-30.
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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.",
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