Human fibroblast growth factor receptor 1-IIIb is a functional fibroblast growth factor receptor expressed in the pancreas and involved in proliferation and movement of pancreatic ductal cells.
OBJECTIVE
The possible functions of the human IIIb-messenger RNA splice variant of fibroblast growth factor (FGF) receptor 1 (FGFR-1 IIIb) are yet to be delineated. In this study, the expression and functionality of the human FGFR-1 IIIb were characterized in the pancreas.


METHODS
In situ hybridization with a specific FGFR-1 IIIb probe in human pancreatic tissues demonstrated that FGFR-1 IIIb localized in normal pancreatic acinar and in ductal-like pancreatic cancer cells. To further assess the potential role of this receptor, a full-length human FGFR-1 IIIb was stably expressed in TAKA-1 pancreatic ductal cells not expressing endogenous FGFR-1.


RESULTS
The FGFR-1 IIIb-expressing TAKA-1 cells synthesized a glycosylated 110-kd protein capable of inducing proliferation on incubation with exogenous FGF-1, -2, and -4. These effects were paralleled by tyrosine phosphorylation of FGFR substrate 2 and association of FGFR substrate 2 with FGFR-1 IIIb. The FGF-1, -2, and -10 induced the activation of p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK, and c-Jun N-terminal kinase. Pharmacological inhibition revealed that FGF-induced proliferation was dependent on the concomitant activation of p44/42 MAPK and c-Jun N-terminal kinase. The FGFR-1 IIIb expression enhanced single-cell movement and plating efficacy.


CONCLUSIONS
Our results demonstrate that the human FGFR-1 IIIb variant is a functional FGFR expressed in the pancreas that can alter pancreatic functions that regulate proliferation, adhesion, and movement.
Liu
Zhanbing
Z
Department of General, Visceral and Transplantation Surgery, University of Ulm, Ulm, Germany.
Ishiwata
Toshiyuki
T
Zhou
Shaxia
S
Maier
Susanne
S
Henne-Bruns
Doris
D
Korc
Murray
M
Bachem
Max
M
Kornmann
Marko
M
D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D005822:Genetic Vectors; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010179:Pancreas / Q000166:cytology / Q000502:physiology*; D010183:Pancreatic Ducts / Q000166:cytology / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000502:physiology*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000502:physiology*
D011494:Protein Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3