ERK/MAPK信号通路激活与乳腺癌细胞浸润性生长的关系

目的：探讨乳腺癌细胞中ERK／MAPK信号转导通路异常激活与乳腺癌细胞浸润性生长的关系及可能机制。方法:采用Western蛋白印迹技术检测乳腺癌细胞系MCF-7和MDA-MB-435S中磷酸化ERK／MAPK(P-ERK)蛋白表达，以及表皮生长因子(EGF)、胰岛素样生长因子-1(IGF-1)和ERK／MAPK通路抑制剂PD98059对两种细胞ERK／MAPK信号转导通路磷酸化的调节。结果:雌激素受体ER(-)的浸润性乳腺癌细胞系MDA-MB-435S中，p-ERK表达明显高于ER( )的非浸润性乳腺癌细胞系MCF-7；EGF可刺激两种细胞p-ERK的表达增加，但这种刺激作用在MDA-MB-435S细胞中更加明显；IGF-1则仅能刺激MCF-7细胞中p-ERK的表达。PD98059能有效阻滞EGF、IGF-1对p-ERK的激活。结论：ERK／MAPK信号转导通路的异常激活与乳腺癌的浸润性生长有关，而EGF可能是异常激活ERK／MAPK信号转导通路，是刺激ER(-)的乳腺癌细胞浸润性生长的重要因素之一。

The relationship between the activation of ERK/MAPK signal transduction pathway and the invasive growth of breast cancer cells

Objective:To address the relationship between ERK/MAPK phosphorylation (p-ERK) and the invasive growth of human breast cancer cells and its possible mechanism. Methods:The protein expressions of p-ERK in human breast cancer cell MCF-7 and MDA-MB- 435s were examined and the regulations of EGF, IGF-1 and ERK/MAP kinase specific inhibitor , PD98059 on these two kinds of cells. Results:Compared with ER-positive and no-invasive MCF-7 cells, the ER-negative and invasive MDA-MB- 435s cells had higher p-ERK protein expression. EGF stimulation induced more p-ERK activation in MDA-MB- 435s cells than that in MCF-7 cells. But IGF-1 only actived p-ERK signal transduction pathway in MCF-7 cells obviously. Treatment with PD98059 could block this activation in the two kinds of cells. Conclusion :The increasing of p-ERK activity was related to the malignant invasive growth of breast cancer cells and EGF was one of the important factors to activate ERK/MAPK signal transduction pathway to promote the cell invasive proliferation.