Kornmann M, Lopez M E, Beger H G, Korc M
Department of Medicine, University of California, Irvine 92697, USA.
Int J Pancreatol. 2001;29(2):85-92. doi: 10.1385/IJGC:29:2:085.
Fibroblast growth factors (FGFs) contribute to angiogenesis and mitogenesis by binding to tyrosine kinase receptors termed FGF receptors (FGFRs). FGF-5 is a secreted FGF that is believed to preferentially act via the IIIc splice variant of FGFR-1. Human pancreatic ductal carcinoma cells express FGF-5 and FGFR-1IIIc, implying a potential for autocrine growth modulation.
In this study we investigated the importance of FGFR-1 IIIc expression for FGF-5 mitogenic signaling in a pancreatic ductal cell line.
A cDNA encoding FGFR-1 IIIc was expressed in the well-differentiated TAKA-1 Syrian hamster pancreatic ductal cell line.
TAKA-1 cells secrete FGF-5, but were found not to express FGFR-1 and to be unresponsive to exogenous FGF-5. In contrast, TAKA-1 clones expressing FGFR-1 IIIc were growth stimulated in the presence of FGF-5 and displayed enhanced mitogen-activated protein kinase (MAPK) activity in the presence of FGF-5. PD98059, an inhibitor of this pathway, inhibited FGF-5-induced growth in these clones.
Our data demonstrate that FGFR-1 IIIc can mediate FGF-5-induced mitogenesis via the MAPK pathway in pancreatic ductal cells, and suggest that expression of FGFR-1 IIIc in conjunction with FGF-5 may contribute to the pathobiology of human pancreatic cancer.
成纤维细胞生长因子（FGFs）通过与称为FGF受体（FGFRs）的酪氨酸激酶受体结合，促进血管生成和有丝分裂。FGF-5是一种分泌型FGF，据信它主要通过FGFR-1的IIIc剪接变体发挥作用。人胰腺导管癌细胞表达FGF-5和FGFR-1IIIc，这意味着存在自分泌生长调节的可能性。
在本研究中，我们调查了FGFR-1 IIIc表达对胰腺导管细胞系中FGF-5有丝分裂信号传导的重要性。
在分化良好的TAKA-1叙利亚仓鼠胰腺导管细胞系中表达编码FGFR-1 IIIc的cDNA。
TAKA-1细胞分泌FGF-5，但未发现表达FGFR-1且对外源FGF-5无反应。相比之下，表达FGFR-1 IIIc的TAKA-1克隆在FGF-5存在下生长受到刺激，并且在FGF-5存在下显示出增强的丝裂原活化蛋白激酶（MAPK）活性。该途径的抑制剂PD98059抑制了这些克隆中FGF-5诱导的生长。
我们的数据表明，FGFR-1 IIIc可通过胰腺导管细胞中的MAPK途径介导FGF-5诱导的有丝分裂，并且表明FGFR-1 IIIc与FGF-5共同表达可能有助于人类胰腺癌的病理生物学过程。
