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EGF调节MT1-MMP和MMP-2的表达及其信号传导机制的研究
引用本文:王丽娜,杜 鹃,李晨曦,杨慧伦,李元博,李 辉,胡海洋,张宗峰. EGF调节MT1-MMP和MMP-2的表达及其信号传导机制的研究[J]. 现代肿瘤医学, 2015, 0(16): 2271-2275. DOI: 10.3969/j.issn.1672-4992.2015.16.08
作者姓名:王丽娜  杜 鹃  李晨曦  杨慧伦  李元博  李 辉  胡海洋  张宗峰
作者单位:哈尔滨医科大学附属第二医院妇产科,黑龙江 哈尔滨 150086
基金项目: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SiHa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。

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

EGF mediates MT1-MMP and MMP-2 expression in SiHa cells through both Pl3-K/AKT and MAPK/ERK pathways
Wang Lina,Du Juan,Li Chenxi,Yang Huilun,Li Yuanbo,Li Hui,Hu Haiyang,Zhang Zongfeng. EGF mediates MT1-MMP and MMP-2 expression in SiHa cells through both Pl3-K/AKT and MAPK/ERK pathways[J]. Journal of Modern Oncology, 2015, 0(16): 2271-2275. DOI: 10.3969/j.issn.1672-4992.2015.16.08
Authors:Wang Lina  Du Juan  Li Chenxi  Yang Huilun  Li Yuanbo  Li Hui  Hu Haiyang  Zhang Zongfeng
Affiliation:Department of Obstetrics and Gynecology,Second Affiliated Hospital,Harbin Medical University,Heilongjiang Harbin 150086,China.
Abstract:Objective:To investigate epidermal growth factor(EGF) mediating signal pathways in the regulation of MT1-MMP and MMP-2 synthesis in SiHa 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 SiHa cells.Furthermore,EGF elevated the activity of MMP-2 in culture media.
Keywords:membrane type 1 matrix metalloproteinase  matrix metalloproteinase 2  epidermal growth factor  mitogen-activated protein kinases  phosphatidylinositol-3 kinase
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