title: Identification of a fibroblast growth factor receptor 1 splice variant that inhibits pancreatic cancer cell growth.
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 NH(2)-terminal kinase. FGFR1-IIIb expression inhibited single-cell movement and in vitro invasion as determined by time-lapse microscopy and Boyden 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.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Ulm, Ulm, Germany.
authors.forename: Zhanbing
authors.initials: Z
authors.lastname: Liu
authors.forename: Nicola
authors.initials: N
authors.lastname: Neiss
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Zhou
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.forename: Max
authors.initials: M
authors.lastname: Bachem
authors.forename: Marko
authors.initials: M
authors.lastname: Kornmann
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020928:Mitogen-Activated Protein Kinases