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
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
复制标题
DOI：
10.1097/mpa.0b013e318053e7e3
复制
发表时间：
2007-08-01
期刊：
影响因子：
2.9
通讯作者：
Kornmann, Marko
中科院分区：
文献类型：
--
作者：
Liu, Zhanbing;Ishiwata, Toshiyuki;Kornmann, Marko
目的：成纤维细胞生长因子（FGF）受体1（FGFR-1 IIIb）的人IIIb信使RNA剪接变体的可能功能尚未被描述。在本研究中，人FGFR-1 IIIb的表达和功能在胰腺中进行了表征。研究方法：用特异性FGFR-1 IIIb探针在人胰腺组织中进行原位杂交，结果表明FGFR-1 IIIb定位于正常胰腺腺泡和导管样胰腺癌细胞中。为了进一步评估该受体的潜在作用，在不表达内源性FGFR-1的TAKA-1胰腺导管细胞中稳定表达全长人FGFR-1 IIIb。结果如下：表达FGFR-1 IIIb的TAKA-1细胞合成糖基化的110-kd蛋白，其能够在与外源FGF-1、FGF-2和FGF-4孵育时诱导增殖。这些作用被FGFR底物2的酪氨酸磷酸化和FGFR底物2与FGFR-1 IIIb的结合所抵消。FGF-1、FGF-2和FGF-10诱导p44/42丝裂原活化蛋白激酶（MAPK）、p38 MAPK和c-Jun N-末端激酶的活化。药理学抑制显示FGF诱导的增殖依赖于p44/42 MAPK和c-Jun N-末端激酶的同时激活。FGFR-1 IIIb表达增强了单细胞运动和平板接种功效。结论：我们的研究结果表明，人FGFR-1 IIIb变体是胰腺中表达的功能性FGFR，其可以改变调节增殖、粘附和运动的胰腺功能。
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 nomial 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.