雌激素及雌激素受体拮抗剂对人乳腺癌细胞MCF-7中雌激素相关受体表达的影响  

Regulation of Orphan Receptor ERRα by Estrogen and Estrogen-Related Receptor Antagonist in MCF-7 Cell Line

作　　者：刘英华[1] 何宁[1] 姜淑卿[1] 李新[1] 张静姝[1] 

机构地区：[1]天津市疾病预防控制中心毒理室,天津300011

出　　处：《环境与健康杂志》2011年第8期677-680,F0003,共5页Journal of Environment and Health

基　　金：天津市卫生局科技基金(09KZ45)

摘　　要：目的通过研究17β-雌二醇(17β-E2)及雌激素受体拮抗剂ICI182,780对人乳腺癌细胞MCF-7中雌激素相关受体(estrogen-related receptor,ERRα)表达的影响,初步探讨ERRα在乳腺癌的发生发展过程中的作用及其与雌激素受体(estrogen receptor,ER)信号通路的关系。方法调整细胞密度为1×106/ml,分别加入DMSO(0.1%)+乙醇(0.1%)(溶剂对照)、17β-E2(1×10-8 mol/L)、17β-E2(1×10-8 mol/L)+ICI182,780(1×10-6 mol/L)作用于细胞24 h,阴性对照组细胞不作任何处理。采用实时定量PCR法检测ERRαmRNA的表达水平,采用免疫细胞化学检测方法及Western Blotting方法检测ERRα蛋白的表达水平。结果与溶剂对照组比较,17β-E2单独染毒组和17β-E2+ICI182,780联合染毒组MCF-7细胞ERRαmRNA及蛋白表达升高,差异有统计学意义(P<0.05);而阴性对照组MCF-7细胞ERRαmRNA及蛋白表达基本无差异(P>0.05)。17β-E2+ICI182,780联合染毒组MCF-7细胞ERRαmRNA及蛋白表达低于17β-E2单独染毒组,差异有统计学意义(P<0.05)。结论雌激素可通过ERα通路介导ERRαmRNA及蛋白的上调;从而诱导下游调节基因的表达,引起乳腺癌细胞的增殖;而ER阻断剂ICI182,780可阻断雌激素对ERRαmRNA及蛋白的上调作用。Objective To investigate the effects of 17β-E2 and ICI182,780 on the expression of ERRα mRNA and protein in MCF-7 Cell line, and to understand the function of ERRα in breast cancer and it＇ s relationship with ERα signaling pathway. Methods The cells were treated with 0.1% DMSO and 0.1% ethanol, 17β-E2 （1×10-8 mol/L）,or with 1×10^-8 mol/L 17β-E2＋1× 104 mol/L ICI182,780 for 24 h, nothing were added into cells of negative control. Quantitative PCR,immunoeytoehemistry and Western Blotting were employed to detect the expression of ERRα mRNA and protein. Results Compared with solvent control,the expression of ERRα mRNA and protein of MCF-7 cells in 17β-E2 treated with 1×10^-8 mol/L 17β-E2 and 1×10^-8 mol/L 17β-E21×10^-6 mol/L ICI182,780 increased significantly. The expression of ERRα mRNA and protein in negative group had no significant difference compared with solvent control. When treated with 1×10^-8 mol/L 1713-E2＋1 ×10^-6 mol/L ICI182,780 in combination, the expression level of ERRα mRNA and protein was significantly lower than that of the group treated with 1 × 10^-8 mol/L 17β-E2 Conclusion ERRα mRNA and protein can be up-regulated by estrogen,and this regulation mediated by ERα, thereby inducing the expression of downstream regulatory genes,causing breast cancer cell proliferation. ICI182,780 can block the induction of 17β-E2.

关 键 词：人乳腺癌细胞 17β- 雌二醇 IC1182 780 雌激素相关受体α 

分 类 号：R994.6[医药卫生—毒理学]