EGF调节MT1-MMP和MMP-2的表达及其信号传导机制的研究  

EGF mediates MT1-MMP and MMP-2 expression in Si Ha cells through both Pl3-K/AKT and MAPK/ERK pathways

作　　者：王丽娜[1] 杜鹃[1] 李晨曦[1] 杨慧伦 李元博[1] 李辉[1] 胡海洋[1] 张宗峰[1] 

机构地区：[1]哈尔滨医科大学附属第二医院妇产科,黑龙江哈尔滨150086

出　　处：《现代肿瘤医学》2015年第16期2271-2275,共5页Journal of Modern Oncology

基　　金：黑龙江省自然科学基金项目(编号:200906);黑龙江省卫生厅科研课题(编号:2009-112);哈尔滨医科大学附属二院博士科研基金(编号:BS2009-15)

摘　　要：目的:探讨表皮生长因子(EGF)在宫颈癌Si Ha细胞中对膜型基质金属蛋白酶(MT1-MMP)和基质金属蛋白酶-2(MMP-2)表达的调节作用,明确其相关的信号传导机制。方法:利用EGF作为干预因素,信号通路阻断剂分别阻断表皮生长因子受体(EGFR)、AKT、ERK、p38和JNK的磷酸化,来观察EGF对MT1-MMP和MMP-2表达的影响及相关信号通路。结果:EGF在mRNA和蛋白水平上诱导MT1-MMP的表达增加和抑制MMP-2的表达;MAPK和ERK激酶抑制剂在mRNA和蛋白水平上可阻断这种诱导;PI3-K抑制剂不影响EGF对MT1-MMP的诱导,但可进一步抑制MMP-2的表达。结论:EGFR通过MAPK/ERK信号通路上调MP1-MMP的表达和下调MMP-2的表达,同时还通过PI3-K/AKT的信号通路轻度上调MMP-2的表达。此外,EGF可以提高细胞培养基中MMP-2的活性。Objective： To investigate epidermal growth factor（ EGF） mediating signal pathways in the regulation of MT1-MMP and MMP-2 synthesis in Si Ha cells,a cervical cancer cell line. Methods： Cells were treated with EGF in the presence or in the absence of inhibitors for EGFR,PI3-K,MEK,and JNK to investigate the effect of EGF on the expression of MT1-MMP and MMP-2 and on the signaling pathways involved in this event. Results： EGF induced the expression of MT1-MMP and inhibited the synthesis of MMP-2 at both the mRNA and protein levels.MT1-MMP and MMP-2 induction were blocked by MAPK or ERK kinase inhibitors. Phosphatidylinositol-3 kinase inhibitors（ PI3-K） did not change the synthesis of MT1-MMP,but further suppressed the expression of MMP-2.Conclusion： EGF receptor up-regulated the expression of MT1-MMP and down-regulated the synthesis of MMP-2 through the MAPK/ERK pathway while concomitantly transmitting a mild positive regulatory signal to the expression of MMP-2 via the PI3-K/AKT pathway in Si Ha cells. Furthermore,EGF elevated the activity of MMP-2 in culture media.

关 键 词：膜型基质金属蛋白酶(MT1-MMP) 基质金属蛋白酶2(MMP-2) 表皮生长因子(EGF) MAPK/ERK PI3-K/AKT 

分 类 号：R737.33[医药卫生—肿瘤]