抑制MTA1对雌二醇调控ER阳性乳腺癌细胞MMP-9、TIMP-1表达的影响

doi:10.11904/j.issn.1002-3070.2014.06.005

实用肿瘤学杂志 ›› 2014, Vol. 28 ›› Issue (6): 503-507.doi: 10.11904/j.issn.1002-3070.2014.06.005

抑制MTA1对雌二醇调控ER阳性乳腺癌细胞MMP-9、TIMP-1表达的影响

王晶¹, 于航¹, 王鹏¹, 谢长英², 倪秀芹³

1.哈尔滨医科大学大庆校区生理教研室(大庆 163319);
2.大庆油田总医院肾内科;
3.哈尔滨医科大学大庆校区解剖教研室

收稿日期:2014-11-07 出版日期:2014-12-28 发布日期:2015-01-08
通讯作者: 王晶,E-mail:wangjing_hmu@126.com
作者简介:王晶,女,(1963-),本科,教授,从事肿瘤药理学方面的研究
基金资助:
黑龙江省科技厅科技攻关项目(GC09C406-4)

Study on the role of MAT1 in estradiol regulated MMP-9,TIMP-1 expression in ER positive breast cancer

WANG Jing¹,YU Hang¹,WANG Peng¹,XIE Changying²,NI Xiuqin³

1.Department of Physiology,Harbin Medical University-Daqing,Daqing 163319,China;
2.Department of Nephrology,Daqing Oilfield General Hospital;
3.Department of Anatomy,Harbin Medical University-Daqing

Received:2014-11-07 Online:2014-12-28 Published:2015-01-08

摘要/Abstract

摘要：

目的观察转移相关蛋白1(Metastasis associated protein 1,MTA1)在雌激素调控雌激素受体(Estrogen Recepto,ER)阳性乳腺癌细胞基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶组织抑制因子(Tissue inhibitor of metalprotease-1,TIMP-1)中的可能作用。方法采用慢病毒转染MTA1-shRNA的方法建立特异性抑制MTA1表达的MCF-7模式细胞株。采用10nM雌二醇(17β-estradiol,E₂)处理细胞48h,Real-time PCR、Western blot分别检测MMP-9、TIMP-1 mRNA与蛋白表达。结果 MTA1-shRNA最大抑制效率为84.9%,提示成功建立了抑制MTA1表达的MCF-7模式细胞株(MCF-7^MTA1-shRNA)。MCF-7野生株(MCF-7^WT)在E₂处理后MMP-9 mRNA和蛋白表达水平分别上升了46%(P＜0.05)和37%(P＜0.05),TIMP-1 mRNA和蛋白表达水平分别降低了32.3%(P＜0.05)和18.2%(P＜0.05);相对MCF-7^WT,MCF-7^MTA1-shRNA MMP-9 mRNA和蛋白表达水平分别降低了42.9%(P＜0.05)和36.7%(P＜0.05),TIMP-1 mRNA和蛋白表达水平未见显著变化;采用E₂处理MCF-7^MTA1-shRNA后,MMP-9 mRNA和蛋白表达水平未见明显变化,TIMP-1 mRNA和蛋白表达水平分别降低了25.4%(P＜0.05)和32.2%(P＜0.05)。结论 MTA1在雌激素上调ER阳性乳腺癌细胞MMP-9表达的信号转导通路中可能发挥重要作用,但未参与雌激素调控ER阳性乳腺癌细胞TIMP-1表达的信号转导通路。

关键词: 乳腺癌, 雌激素, 转移相关蛋白1, 基质金属蛋白酶-9, 金属蛋白酶组织抑制因子-1

Abstract:

Objective To investigate the role of metastasis associated protein 1(MTA1)in estrogen regulated expression of matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalprotease-1(TIMP-1)in estrogen receptor (ER)positive breast cancer cells.Methods MTA1 knockdown cell model was generated based on MCF-7 breast cancer cell line by transfected with MTA1-shRNA.The mRNA and protein level of MMP-9 and TIMP-1 in wild type MCF-7(MCF-7^WT)and MCF-7^MTA1-shRNA before and after 17β-estradiol(E₂)treatment were examined by Real-time PCR and Western blot respectively.Results The MTA1-shRNA showed maximally 84.9% suppression of MTA1 expression in MCF-7,suggesting a satisfied MTA1 knockdown cell model was established for subsequent experiments.After treated with E₂ for 48h,MCF-7^WT showed an increment of 46%(P＜0.05)and 37%(P＜0.05)of the mRNA and protein level of MMP-9 and a decrement of 32.3%(P＜0.05)and 18.2%(P＜0.05)of TIMP-1;MCF-7^MTA1-shRNA showed a decrement of 32.3%(P＜0.05)and 18.2%(P＜0.05)of mRNA and protein expression of MMP-9 respectively but no significant difference in TIMP-1 comparing with MCF-7^WT before treated with Estradiol.After E₂ treatment,MCF-7^MTA1-shRNA didn′t show significant change of MMP-9 except decrements of 32.3%(P＜0.05)and 18.2%(P＜0.05)in the mRNA and protein levels of TIMP-1.Conclusion MTA1 may be involved in the pathway by which estrogen regulated the expression of MMP-9 but not TIMP-1 in ER positive breast cancer cells.

Key words: Breast cancer, Estrogen, Metastasis-associated protein 1, Matrix metalloproteinase-9, Tissue inhibitor of metalloproteinases-1

中图分类号:

R73-3

王晶, 于航, 王鹏, 谢长英, 倪秀芹. 抑制MTA1对雌二醇调控ER阳性乳腺癌细胞MMP-9、TIMP-1表达的影响[J]. 实用肿瘤学杂志, 2014, 28(6): 503-507.

WANG Jing,YU Hang,WANG Peng,XIE Changying,NI Xiuqin. Study on the role of MAT1 in estradiol regulated MMP-9,TIMP-1 expression in ER positive breast cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2014, 28(6): 503-507.

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抑制MTA1对雌二醇调控ER阳性乳腺癌细胞MMP-9、TIMP-1表达的影响

Study on the role of MAT1 in estradiol regulated MMP-9,TIMP-1 expression in ER positive breast cancer

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