Acidic fibroblast growth factor (FGF-1) signaling inhibits peroxynitrite-induced cell death during pancreatic tumorigenesis

Free Radical Biology & Medicine
S M VickersJ A Thompson

Abstract

Previous immunohistochemical studies have demonstrated enhanced appearance of FGF-1 and nitrotyrosine, a footprint of reactive nitrogen species peroxynitrite (ONOO(-)), in human pancreatic adenocarcinoma. We have examined the consequences of constitutive exposure to FGF-1 in nontumorigenic rat ductal epithelial cells (ARIP). ARIP cells were transduced with either a secreted chimera of FGF-1, ARIP(FGF-1), or a control plasmid, 65 RIP(betag). These cells were evaluated for alteration in growth and morphology, responses to ONOO(-) (protein tyrosine nitration/phosphorylation), and in vivo tumor formation. ARIP(FGF-1) cells, in contrast to 65 RIP(betag), demonstrated a transformed morphology, a 2-fold increased growth rate, and enhanced protein tyrosine phosphorylation. Treatment with 150 microM ONOO(-) resulted in 86 and 7% (p <.01) death of ARIP(betag) and ARIP(FGF-1), respectively. Exposure of 65 RIP(betag) cells to ONOO(-) enhanced tyrosine phosphorylation and tyrosine nitration of several polypeptides. Cell signaling by FGF-1 enhanced both phosphorylation and nitration of tyrosine residues in target proteins modified by ONOO(-). ARIP(betag) cells failed to exhibit tumor formation in nude mice, but at d 7 in vivo cells were TUNE...Continue Reading

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Citations

Nov 1, 2003·Archives of Biochemistry and Biophysics·Patricia BagnascoJohn A Thompson
Feb 8, 2003·Archives of Biochemistry and Biophysics·Jing JiaoJohn A Thompson
Oct 5, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·S S KelpkeJ A Thompson
Nov 20, 2004·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Anna S Gukovskaya, Stephen J Pandol
Jul 6, 2004·The Journal of Surgical Research·Peter BüchlerOscar J Hines
Nov 18, 2005·Nitric Oxide : Biology and Chemistry·Doanh C TranHo-Leung Fung
Apr 5, 2019·Cell Proliferation·Xiaodiao KangZhi-Wei Wang

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