基因沉默孤儿核受体ERRα抑制前列腺癌细胞的体内转移

Knockdown ERRα Inhibits in Vivo Metastasis in Prostate Cancer Cells

目的:研究孤儿核受体ERRα对前列腺癌细胞E-cadherin(上皮细胞钙粘蛋白)的表达水平和体内转移能力的影响。方法:利用慢病毒介导的sh RNA构建稳定下调ERRα表达的DU145-sh ERRα和PC-3M-sh ERRα前列腺癌细胞模型,同时用ERRα特异性抑制剂XCT790抑制其活性,并利用Western Blotting(免疫印迹)检测上皮细胞标志物E-cadherin的表达水平。将PC-3M-sh ERRα细胞和PC-3M-scramble对照细胞用荧光素酶标记后原位注射小鼠前列腺,8周以后通过体内成像系统检测原位瘤的形成及其体内转移情况。结果:基因沉默ERRα表达水平和用其特异性抑制剂XCT790处理DU145后,E-cadherin的表达水平明显降低。在PC-3M-sh ERRα细胞中,E-cadherin的表达水平明显低于对照组,同时由其构建的6只原位前列腺癌小鼠模型中没有发生转移,而由对照组细胞构建的7只原位前列腺癌小鼠模型中有4只发生了转移。结论:在前列腺癌细胞中下调ERRα的表达水平抑制其E-cadherin的表达和体内转移能力。

Objective： To explore the roles of orphan nuclear receptor ERRα in E-cadherin expression regulation and in vivo metastasis in prostate cancer cells. Methods： DU145-shERRα and PC-3M-shERRα cell models were established by gene knockdown mediated by lentivirus. ERRct specifc antaguist XCT790 was used to inhibit its activity, the expression level of E-cadherin was identified by Western Blotting. PC-3M-shERRα and PC-3M-scramble cells were labeled by luciferase and injected in situ in mice prostate, metastases were measured through in vivo image system and indicated by the fluorescence intensity 8 weeks after injection. Results： The expression level of E-cadherin was significantly decreased in DU145 after knockdown ERRαor treatment with XCT790. The expression level of E-cadherin in PC-3M-shERRα was significantly suppressed as compared to that in control cells. Moreover, 4 of 7 in situ prostate cancer mice models dreived from PC-3M-scramble cells, while 0 of 6 from PC-3M-shERRα cells, develop metastases. Conclusions： Knockdown ERRα in prostate cancer cells attenuate E-cadherin expression and their in vivo metastasis.