雌激素相关受体α与雌激素受体α通路相关性研究  

Correlation between estrogen receptor-related receptor α and estrogen receptor α pathway

作　　者：刘英华[1] 何宁[1] 姜淑卿[1] 张静姝[1] 

机构地区：[1]天津市疾病预防控制中心,天津300011

出　　处：《中华肿瘤防治杂志》2013年第17期1306-1309,1314,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：天津市卫生局科技基金(09KZ45)

摘　　要：目的:探讨雌激素相关受体α(estrogen-related receptorα,ERRα)与雌激素受体α(estrogen receptors alpha,ERα)经典通路的关系。方法:采用蛋白质印迹法观察雌二醇(E2)、ICI182、780及XCT790对MCF-7细胞中ERRα、ERα和TFF1蛋白表达的影响;Real-time RT-PCR检测MCF-7细胞中ERRα、ERα和TFF1mRNA表达水平的变化。结果:E2诱导后ERα由(100.0±0.0)%增加至(240.0±27.0)%,ERRα由(100.0±0.0)%增加至(244.2±35.9)%,TFF1mRNA由(100.0±0.0)%增加至(201.7±21.6)%;ERα蛋白的表达由(100.0±0.0)%增加至(128.4±5.3)%,ERRα蛋白的表达由(100.0±0.0)%增加至(157.3±5.6)%,TFF1蛋白的表达由(100.0±0.0)%增加至(133.2±7.1)%,表明E2可上调这3种基因的表达。ICI182、780作用后ERα、ERRα和TFF1mRNA表达量分别为(133.6±6.9)%、(168.1±26.8)%和(138.9±12.9)%,蛋白表达量分别为(84.2±5.0)%、(100.0±7.5)%和(84.9±5.7)%,表明ICI182、780可抑制E2对ERRα、ERα和TFF1的诱导作用。XCT790作用后ERRα和TFF1 mRNA表达量分别为(136.8±28.2)%和(140.4±11.4)%,ERα、ERRα和TFF1蛋白表达量分别为(76.4±5.3)%、(90.7±6.9)%和(76.3±6.6)%,表明ICI182、780和XCT790均对E2诱导的ERα、ERRα、TFF1 mRNA和蛋白上调有抑制作用。ICI182、780与XCT790联合作用后,ERα、ERRα和TFF1mRNA表达量分别为(98.4±17.2)%、(108.7±8.8)%和(95.1±21.6)%,蛋白表达量分别为(58.2±6.7)%、(63.2±6.0)%和(57.1±5.9)%,表明两种阻断剂联合作用对这种上调的抑制作用大于二者单独的抑制作用。结论:E2对ERRα的诱导作用是通过ER介导的,将ERα和ERRα联合应用作为分子生物学指标及靶标,对乳腺癌内分泌治疗策略的实施可能有其临床意义。OBJECTIVE： To investigate the relationship of ERRα with the the ERa classic pathway. METHODS： After MCF-7 cells was treated with E2 ,ICI182,780 and XCT790 , ERRα,ERα and TFFlexpression in MCF-7 cells were determined using Western bloting and quantitative PCR. RESULTS： After induced with E2 , the expression rate of ERα increased from （100.0±0.0）% to （240.0±27. 0）%,the rate of ERRα increased from （100.0±0.0）% to （244. 2±35.9） % ,the rate of TFF1 mRNA increased from （100.0±0.0） % to （201.7±21.6） %. The expression rate of ERa protein increased from （100.0±0.0）% to （128.4＋5.3）% ,the rate of ERRα protein increased from （100.0±0.0）% to （157.3±5.6） % ,and the rate of TFF1 protein increased from （100.0±0.0） % to （133.2±7.1） %. The results indicated that E2 upregulate the expression rate of ERα, ERRα and TFF1. ICI182,780 reduced the expression rate of mRNA to （133.6±6.9） %, （168.1±26.8）% and （138.9±12.9）% respectively. The expression rate of protein reduced to （84.2± 5.0） %, （100.0±7.5）% and （84.9±5.7）% respectively,which indicated that ICI182,780 inhibited the increasing effect of E2. After exposed to XCT790 for 48 hours,the expression rate of ERRa and TFF1 mRNA reduced to （136.8±28.2） % and （140.4±11.4）%. The expression rate of ERa, ERRa and TFF1 protein reduced to （76.4± 5.3）%, （90.7± 6.9）% and （76.3± 6.6）% respectively,which indicated that ICI182,780 and XCT790 inhibited the increasing effect of E2. Combined XCT790 and ICI182,780 treatment for 48 hours, the expression rate of mRNA was （98.4 ± 17.2）%, （108. 7 ±8.8） % and （95. 1±21. 6）% respectively. The expression rate of protein was （58. 2 ± 6. 7）%, （63. 2 ±6. 0）M and （57.1±5.9） % respectively. The Synergistic effects of ICI182,780 and XCT790 were greater than that treatd with themselves. CONCLUSION： The effect of E2 on ERRα is mediated by ER;Combined application of ERRα and ERα as biomarker and target may

关 键 词：乳腺肿瘤 17Β-雌二醇 雌激素受体Α 雌激素相关受体Ⅱ TFF1 

分 类 号：R737.9[医药卫生—肿瘤]