成纤维细胞生长因子受体1在胰腺癌细胞中的表达和调控

Regulation of pancreatic cancer cells by fibroblast growth factor receptor-1

目的研究成纤维细胞生长因子受体1（FGFR1）蛋白和mRNA在胰腺癌细胞系中的表达和调控机制。方法采用Western免疫印迹实验、Northern印迹分析和RT—PCR检测FGFR1在胰腺癌细胞中的表达。使用外源性生长因子刺激细胞并使用激酶抑制剂阻断细胞内信号转导通路，观察FGFR1蛋白和mRNA在胰腺癌细胞中表达的变化情况。结果FGFR1蛋白和mRNA在胰腺癌细胞系中均有不同程度的表达。生长因子刺激可上调FGFR1蛋白和mRNA的表达水平。其中IGF-1、EGF和FGF2显著增加MiaPaCa-2细胞FGFR1的表达，EGF和FGF2显著增加PANC-1细胞FGFR1的表达（P〈0．05）。FGF2对FGFR1表达的调节具有时间依赖性。ERK1／2抑制剂U0126和p38MAPK抑制剂SB203580降低了PANC-1细胞中FGFR1的蛋白和mRNA的表达水平。结论生长因子可上调FGFR1在胰腺癌细胞中的表达水平，MAPK信号转导通路中的ERK1／2和p38MAPK亚通路参与FGFR1表达的调节。

Objective To investigate the expression and regulation of FGFR1 protein and mRNA in human pancreatic cancer cell lines. Methods The expressions of FGFR1 protein and mRNA in pancreatic cancer cells were tested by Western blot, Northern blot and RT-PCR. The effects of exogenous growth factors and tyrosine kinase inhihitors on expression of FGFR1 protein and mRNA was observed. Results FGFR1 protein and mRNA expressed in 7 pancreatic cancer cell lines in different levels. After stimulation of several exogenous growth factors, we found that IGF-1, EGF and FGF2 up-regulated the expression of FGFR1 in Mia PaCa-2 siguificanfly; EGF and FGF2 up-regulated the expression of FGFR1 in PANC-1 significantly （P 〈0. 05）. The effect of FGF2 on the expression of FGFR1 was in time-dependent manner. ERK1/2 special inhibitor UO126 and p38 MAPK special inhibitor SB203580 down-regulated the expression of FGFR1. Conclusion Expression of FGFR1 is up-regulated by growth factors and may be modulated through ERK1/2 and p38 MAPK signal transduction pathway.