Sun P-M, Gao M, Wei L-H, Mustea A, Wang J-L, Könsgen D, Lichtenegger W, Sehouli J
Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, People's Republic of China.
Int J Gynecol Cancer. 2006;16 Suppl 2:564-8. doi: 10.1111/j.1525-1438.2006.00697.x.
Estrogen receptor-related receptor alpha (ERRalpha) was reported to compete with estrogen receptor alpha (ERalpha) in a constitutive manner as an orphan nuclear closely related to (ERalpha). To discuss the role of ERRalpha in the endometrial carcinoma cells, this study was performed. ER-responsive endometrial carcinoma cells Ishikawa and ER-nonresponse HEC-1A cells were treated with different concentration of 17beta-E2 or E2 plus ICI 182780. Semiquantitative reverse transcription-polymerase chain reaction and western blot were performed to analysis the expression of human estrogen receptor-related receptor alpha (hERRalpha). Plasmid PLXSN-hERRalpha was constructed and transfected into cells. Selected in the medium containing high-dose G418, the Ishikawa and HEC-1A cells with stable overexpression of hERRalpha were constructed and renamed as Ishikawa/hERRalpha and HEC-1A/hERRalpha, respectively. To discuss the effect of overexpression of hERRalpha in the cell biological behavior (3-[4,5-dimethylth-lazol-2yl]-2,5-diphenyltetrazolium bromid) (MTT) cell assay was performed. Estrogen downregulates ERRalpha expression in ER-positive Ishikawa cells, while upregulates the expression of ERRalpha in ER-negative HEC-1A cells. In Ishikawa cells, the downregulation of 17beta-E2 in ERRalpha expression cells could be blocked by ICI 182780. A decreasing expression of hERalpha was observed in the ER-responsive cells with overexpression of ERRalpha (Ishikawa/hERRalpha). Overexpression of hERRalpha inhibits the cell proliferation in the ERalpha-responsive Ishikawa cells and stimulated the cell proliferation in the ERalpha-nonresponsive HEC-1A cells. Function of hERRalpha depends on the expression and function of hERalpha. ER-mediated signaling might be the important factor resulting in the hormone-dependent endometrial carcinoma, whereas ERRalpha-mediated pathway might act as the vital role in hormone-independent endometrial carcinoma.
据报道，雌激素受体相关受体α（ERRα）作为一种与雌激素受体α（ERα）密切相关的孤儿核受体，以组成型方式与ERα竞争。为探讨ERRα在子宫内膜癌细胞中的作用，开展了本研究。用不同浓度的17β-雌二醇或雌二醇加ICI 182780处理雌激素反应性子宫内膜癌细胞系Ishikawa和雌激素无反应性的HEC-1A细胞。采用半定量逆转录-聚合酶链反应和蛋白质免疫印迹法分析人雌激素受体相关受体α（hERRα）的表达。构建质粒PLXSN-hERRα并转染至细胞中。在含高剂量G418的培养基中筛选，构建了稳定过表达hERRα的Ishikawa和HEC-1A细胞，分别命名为Ishikawa/hERRα和HEC-1A/hERRα。为探讨hERRα过表达对细胞生物学行为的影响，进行了（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐）（MTT）细胞实验。雌激素下调雌激素受体阳性的Ishikawa细胞中ERRα的表达，而上调雌激素受体阴性的HEC-1A细胞中ERRα的表达。在Ishikawa细胞中，ICI 182780可阻断17β-雌二醇对ERRα表达细胞的下调作用。在ERRα过表达的雌激素反应性细胞（Ishikawa/hERRα）中观察到hERα表达降低。hERRα过表达抑制雌激素受体α反应性的Ishikawa细胞的增殖，并刺激雌激素受体α无反应性的HEC-1A细胞的增殖。hERRα的功能取决于hERα的表达和功能。雌激素受体介导的信号传导可能是导致激素依赖性子宫内膜癌的重要因素，而ERRα介导的途径可能在激素非依赖性子宫内膜癌中起关键作用。
