Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth

Zhanbing Liu, Nicola Neiss, Shaoxia Zhou, Doris Henne-Bruns, Murray Korc, Max Bachem, Marko Kornmann

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Fibroblast growth factor receptors (FGFR) play important roles in many biological processes. Nothing is presently known about possible roles of the human FGFR1-IIIb mRNA splice variant. In this study, we characterized for the first time the effects of FGFR1-IIIb expression on the transformed phenotype of human pancreatic cancer cells. The full-length FGFR1-IIIb cDNA was generated and stably expressed in PANC-1 and MIA PaCa-2 pancreatic cancer and TAKA-1 pancreatic ductal cells. FGFR1-IIIb-expressing cells synthesized a glycosylated 110-kDa protein enhancing tyrosine phosphorylation of FGFR substrate-2 on FGF-1 stimulation. The basal anchorage-dependent and anchorage-independent cell growth was significantly inhibited. These effects were associated with a marked reduction of p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in combination with enhanced activity of p38 MAPK and c-Jun NH2-terminal kinase. FGFR1-IIIb expression inhibited single-cell movement and in vitro invasion as determined by time-lapse microscopy and Hoyden chamber assay as well as in vivo tumor formation and growth in nude mice. Microscopic analysis of the xenograft tumors revealed a reduced Ki-67 labeling and a lower amount of tumor necrosis in FGFR1-IIIb-expressing tumors. Our results show that FGFR1-IIIb is a functional FGFR that inhibits the transformed phenotype of human pancreatic cancer cells.

Original languageEnglish (US)
Pages (from-to)2712-2719
Number of pages8
JournalCancer Research
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2007
Externally publishedYes

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Receptor, Fibroblast Growth Factor, Type 1
Pancreatic Neoplasms
Growth
Fibroblast Growth Factor Receptors
Neoplasms
Receptor, Fibroblast Growth Factor, Type 2
Phosphorylation
Phenotype
Biological Phenomena
Fibroblast Growth Factor 1
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Heterografts
Nude Mice
Cell Movement
Tyrosine
Microscopy
Necrosis
Complementary DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth. / Liu, Zhanbing; Neiss, Nicola; Zhou, Shaoxia; Henne-Bruns, Doris; Korc, Murray; Bachem, Max; Kornmann, Marko.

In: Cancer Research, Vol. 67, No. 6, 15.03.2007, p. 2712-2719.

Research output: Contribution to journalArticle

Liu, Z, Neiss, N, Zhou, S, Henne-Bruns, D, Korc, M, Bachem, M & Kornmann, M 2007, 'Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth', Cancer Research, vol. 67, no. 6, pp. 2712-2719. https://doi.org/10.1158/0008-5472.CAN-06-3843
Liu, Zhanbing ; Neiss, Nicola ; Zhou, Shaoxia ; Henne-Bruns, Doris ; Korc, Murray ; Bachem, Max ; Kornmann, Marko. / Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth. In: Cancer Research. 2007 ; Vol. 67, No. 6. pp. 2712-2719.
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