中文摘要：

背景与目的：雌激素受体相关受体α（estrogen receptor-related receptor α，ERRα）是孤儿核受体亚家族成员之一，可与雌激素受体α（estrogen receptor α，ERα）竞争结合同一靶基因位点，从而干扰雌激素-雌激素受体核内信号通路的转导，因而可能在子宫内膜癌的发生方面发挥一定作用。本研究旨在探讨17β-雌二醇（E2）对子宫内膜癌细胞孤儿核受体ERRα的调控作用，明确ERRα在子宫内膜癌发生中的作用及与ER信号通路的关系。方法：采用RT-PCR和Western blot方法，检测不同浓度17β-E2（10^-10、10^-8、10^-6mol／L）作用于ERα阳性的子宫内膜癌细胞系Ishikawa细胞和ERα阴性的子宫内膜癌细胞系HEC-IA细胞24h、48h后ERRα mRNA水平和蛋白水平的变化．并应用完全性ER拮抗剂IC1182780同时作用细胞，观察是否可阻断E2对ERRα的调控作用。结果：不同浓度的1713，E2作用于Ishikawa细胞24h、48h后ERRα mRNA水平及蛋白水平均有不同程度的下调，以10^-8mol／L作用后下调最明显。同时加入10^-8mol／L E2和10^-6mol／L IC1182780作用于Ishikawa细胞后，E2对ERRor的下调作用被阻断。不同浓度的17β-E2作用于HEC-IA细胞24h后ERRα mRNA水平出现不同程度上调．但蛋白水平未见明显变化。当17β-E2作用细胞48h后，ERRα蛋白水平出现明显上调．以10^-8mol／L作用后上调最明显。同时加入10^-8mol／L E2和10^-6mol／L ICI182780作用于HEC-IA细胞后，E2对ERRα的上调作用无明显变化。结论：17β-E2可下调Ishikawa细胞ERRα的表达，且这种降调作用是通过ER介导完成的；17β-E2可上调HEC-IA细胞ERRα的表达．且这种上调作用不被完全性ER拮抗剂ICI182780所阻断。

英文摘要：

BACKGROUND ＆ OBJECTIVE. Estrogen receptor-related receptor α （ERRα）, a member of the subfamily of orphan nuclear receptors, could compete with estrogen receptor α （ERα） to bind the same target genes and interfere in ER signal pathway. Therefore, it might be associated to the tumorigenesis of endometrial carcinoma. This study was to explore the regulatory effect of 17β-estradiol （17β-E2） on ERRα expression, and to elucidate the relationship between ERRα and ER signal pathway in endometrial carcinoma cell lines. METHODS. ERα-positive cell line Ishikawa and ERa-negative cell line HEC-IA were treated with different concentrations of 17β-E2 （1×10^-10 mol/L, 1×10^-8 mol/L, and 1×10^-8mol/L） for 24 h and 48 h, respectively. The levels of ERRα mRNA and protein were examined by reverse transcription-polymerase chain reaction （RT-PCR） and Western blot. 17β-E2 （1×10^-8 mol/L） and complete ER inhibitor ICI182,780 （1×10^-6mol/ L） were given concomitantly to observe the change of ERRα expression. RESULTS. The levels of ERRα mRNA and protein in Ishikawa cells were down-regulated after stimulated for 24 h and 48 h by different concentrations of 17β-E2. The maximal effect was observed at the concentration of 1×10^-8mol/L. When 17β-E2 and ICI182,780 were given simultaneously to Ishikawa cells, this down-regulation was blocked. However, the level of ERRα mRNA, not protein, in HEC-IA cells was up-regulated after stimulated by different concentrations of 17β-E2 for 24 h. After stimulated by 17β-E2 for 48 h, the level of ERRα protein was up-regulated, which could not be blocked by ICI182,780. CONCLUSIONS： 17β-E2 can down-regulate the expression of ERRα in Ishikawa cells, which is mediated by ERα. 17β-E2 can up-regulate the expression of ERRα in HEC-IA cells, but this regulation cannot be blocked by ICI182,780.