雌二醇对三阴乳腺癌细胞integrin β4水解作用的影响  

The Proteolysis of Integrin β4 in Triple Negative Breast Cancer Cell is Enhanced by Estradiol via GPR30

作　　者：陈腾祥[1] 严莉莎 霍建云 张金娟[2] 潘娅[1] 王晋星一[1] 陈妮[1] 臧贵勇[3] 胡晓霞[1] 

机构地区：[1]贵阳医学院生理学教研室,贵州贵阳550004 [2]贵阳医学院机能学实验室,贵州贵阳550004 [3]贵阳医学院人体解剖学教研室,贵州贵阳550004

出　　处：《贵阳医学院学报》2015年第1期10-12,23,共4页Journal of Guiyang Medical College

基　　金：国家自然科学基金资助项目(NO.81060176);贵阳医学院院基金(院基金合同字第2012005号);贵州省高层次人才科研条件特助经费(TZJF-2009年38号)

摘　　要：目的:研究三阴乳腺癌(TNBC)MDA-MB-231细胞中雌二醇对整合素(integrin)β4水解的促进作用。方法:常规培养MDA-MB-231细胞至指数增长期,分别给予17β-雌二醇、雌激素受体(ER)特异性阻断剂4-羟基他莫西芬(OHT)和G蛋白偶联受体30(GPR30)特异性阻断剂G-15干预30 min,采用蛋白质印迹(Western blot)实验检测钙激活中性蛋白酶2(calpain 2)的表达和integrinβ4水解的情况。结果:17β-estradiol在短时间内可促进MDA-MB-231细胞130和95k D integrinβ4水解片段的产生,促进作用呈浓度依赖方式,而对calpain 2表达没有明显影响;4-OHT不能阻断17β-estradiol对integrinβ4的水解作用,且其本身可促进integrinβ4水解;G-15能阻断17β-estradiol对integrinβ4的水解。结论:在TNBC MDA-MB-231细胞中,17β-estradiol可通过GPR30促进130和95k Dintegrinβ4水解片段的产生。Objective： To investigate the way of estrogen to enhance the proteolysis of integrin β4 in triple negative breast cancer （TNBC） cell, MDA-MB-231. Methods： MDA-MB-231 was treated with 17β-estradiol , 4-hydroxytamoxifen（OHT） and G-15 for 30 rain respectively or jointly when the cell reached to exponential growth stage. Then, Western blot was used to detect the proteolysis of integrin β4 and the expression of calpain 2. Results： As Western blot results showing, not the expression of ealpain 2, but the hydrolysis products of integrin β4 with molecular weight of 130 kD and 95kD were raised by 17β-estradiol in a short time with dose-dependent way. However, an estrogen receptor （ER） specific inhibitor could enhance, instead of block, the proteolysis function of 17β-estradiol to integrin β4, which could be blocked by the specific inhibitor of G-coupled protein receptor （GPR） 30, G-15. Conclusion： In TNBC cell, MDA-MB-231, the hydrolysis products of integrin β4 with 130 and 95 kD are enhanced by 17β-estradiol via GPR30.

关 键 词：三阴乳腺癌 整合素β4 钙激活中性蛋白酶2 17β-雌二醇 4-羟基他莫西芬 G蛋白偶联受体30 

分 类 号：R737.9[医药卫生—肿瘤] R733.7[医药卫生—临床医学]