Kornmann M, Ishiwata T, Matsuda K, Lopez ME, Fukahi K, Asano G, Beger HG, Korc MThe IIIc isoform of fibroblast growth factor receptor 1 is overexpressed in human pancreatic cancer and enhances tumorigenicity of hamster ductal cells. Gastroenterology 123: 301-313

Department of General Surgery, University of Ulm, Ulm, Germany.
Gastroenterology (Impact Factor: 16.72). 07/2002; 123(1):301-13. DOI: 10.1053/gast.2002.34174
Source: PubMed


Fibroblast growth factors (FGFs) are mitogenic polypeptides that signal via FGF receptors (FGFRs). Pancreatic ductal adenocarcinomas (PDACs) overexpress multiple FGFs, implying a potential for growth modulation. In this study we investigated the importance of the IIIc splice variant of FGFR-1 (FGFR-1 IIIc) in PDAC.
Expression of FGFR-1 IIIc was determined by a ribonuclease protection assay in pancreatic cancer cell lines and in tissues. In situ hybridization was used to localize FGFR-1 IIIc messenger RNA (mRNA) in pancreatic tissues. A cDNA encoding FGFR-1 IIIc was stably transfected into the well-differentiated TAKA-1 pancreatic ductal cell line that is not responsive to FGF5 and does not express FGFR-1.
FGFR-1 IIIc was expressed in 5 of 7 pancreatic cancer cell lines and in the majority of the cancer cells in 4 of 7 PDAC samples. In vitro, TAKA-1 cells stably transfected with FGFR-1 IIIc exhibited increased basal growth; enhanced basal tyrosine phosphorylation of FGFR substrate-2 (FRS2), Shc, and phospholipase Cgamma; and increased activation of mitogen-activated protein kinase (MAPK). PD98059, an inhibitor of MAPK, suppressed the basal growth of parental and transfected clones, but the effect was more marked in clones expressing FGFR-1 IIIc. In vivo, tumor formation in nude mice was dramatically enhanced with FGFR-1 IIIc transfected (20 of 20) in comparison with sham transfected (0 of 10) cells.
Our data indicate that FGFR-1 IIIc is expressed in human pancreatic cancer cells, promotes mitogenic signaling via the FRS2-MAPK pathway, and has the potential to enhance pancreatic ductal cell transformation.

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    • "We recently showed that over-expression of FGFR1-IIIb in PDAC cells reverted the malignant phenotype inhibiting proliferation, single cell movement , and migration in vitro, as well as xenograft formation and growth in vivo (Liu et al, 2007b). On the other hand, it is well known that over-expression of FGFR1-IIIc enhances the malignant phenotype of PDAC (Wagner et al, 1998; Kornmann et al, 2002). FGFR1-IIIb over-expression in PDAC cells resulted in strong p38-MAPK and JNK activitation (Liu et al, 2007a, b). "
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