Abstract
OBJECTIVES: 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 ductallike 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 147-157 |
| Number of pages | 11 |
| Journal | Pancreas |
| Volume | 35 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2007 |
| Externally published | Yes |
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Keywords
- Fibroblast growth factor
- Mitogen-activated protein kinase
- Pancreas
- Signaling cascades
- Tyrosine kinase receptor
ASJC Scopus subject areas
- Gastroenterology
- Endocrinology
Cite this
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. / Liu, Zhanbing; Ishiwata, Toshiyuki; Zhou, Shaxia; Maier, Susanne; Henne-Bruns, Doris; Korc, Murray; Bachem, Max; Kornmann, Marko.
In: Pancreas, Vol. 35, No. 2, 08.2007, p. 147-157.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Liu, Zhanbing
AU - Ishiwata, Toshiyuki
AU - Zhou, Shaxia
AU - Maier, Susanne
AU - Henne-Bruns, Doris
AU - Korc, Murray
AU - Bachem, Max
AU - Kornmann, Marko
PY - 2007/8
Y1 - 2007/8
N2 - OBJECTIVES: 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 ductallike 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.
AB - OBJECTIVES: 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 ductallike 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.
KW - Fibroblast growth factor
KW - Mitogen-activated protein kinase
KW - Pancreas
KW - Signaling cascades
KW - Tyrosine kinase receptor
UR - http://www.scopus.com/inward/record.url?scp=34447515431&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447515431&partnerID=8YFLogxK
U2 - 10.1097/mpa.0b013e318053e7e3
DO - 10.1097/mpa.0b013e318053e7e3
M3 - Article
VL - 35
SP - 147
EP - 157
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 2
ER -