过表达ER恢复雌激素对子宫内膜癌KLE细胞中Notch信号通路的调控  

Effect of Extra-expression of Estrogen Receptor in Restoration of Regulation of Estrogen on Notch Signaling Pathway in Endometrial Cancer Cells

作　　者：魏桠楠[1] 周冬梅[1] 吴凌[1] 杨婷[1] 祝颖[1] 冯怡雯[1] 张箴波[1] 祝亚平[1] 丰有吉[1] 

机构地区：[1]上海交通大学附属上海市第一人民医院,上海200080

出　　处：《现代生物医学进展》2011年第16期3001-3004,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金(81001155和81020108027);上海市卫生局面上项目(2009028)

摘　　要：目的:通过观察雌激素对子宫内膜癌KLE细胞中Notch信号通路的影响,探讨过表达雌激素核受体(estrogen receptor,ER)是否可以恢复雌激素对Notch信号通路的调控作用,继而调节细胞增殖活性。方法:MTT检测雌激素及Notch信号通路对细胞增殖活性的影响;RT-PCR及Western-blotting检测雌激素及Notch通路抑制剂DAPT对Notch表达的影响;质粒的抽提及转染使KLE细胞中的雌激素核受体ER过表达。结果:雌激素呈剂量依赖效应促进KLE细胞的增殖活性,其中以雌激素浓度为1.0×10^(-9)M时最明显(相对于对照组为1.25±0.026,P<0.05);抑制Notch信号通路的表达可以明显下调KLE细胞的增殖活性(0.76±0.02,P<0.05);在KLE细胞中,雌激素对Notch的表达没有明显的调控作用,但是将其雌激素核受体过表达后,雌激素可明显上调Notch的表达,并显著促进细胞的增殖活性(1.24±0.02,P<0.05)。结论:在ER阴性的子宫内膜癌细胞中过表达ER,可以恢复雌激素对Notch信号通路的调控,从而进一步的调控细胞增殖活性。Objective： To observe the effect of estrogen on Notch signaling pathway in endometrial cancer cells, and to explore whether estrogen can induce the expression of Notch when estrogen receptor （ER） is up-regulated, further affecting the cell proliferation. Methods： MTT was used to measure the proliferative activity after various treatments. RT-PCR and Western-blotting were used to determine the effect of estrogen and DAPT on Notch expression in mRNA and protein levels. Plasmid was transfected into KLE to induce the expression of estrogen receptor. Results： Estrogen enhances endometrial cancer cells＇ proliferative activity, especially with the concentration of 1.0×10-9M （1.25±0.026, P〈0.05）. Inhibition of Notch signal pathway blocks estrogen induced cellular growth （0.76±0.02, P〈0.05）. Expression of Notch is not changed by estrogen but up-rcguiated after transfection. Further more, the relative proliferative activity is enhanced （1.24±0.02, P〈0.05）. Conclusions： In ER-negative, endometrial cancer cells KLE, estrogen can activate Notch signal pathway when ER is up-regulated, and then enhance cells＇ proliferative activity.

关 键 词：KLE 雌激素 NOTCH信号通路 增殖活性 核受体 

分 类 号：R737.33[医药卫生—肿瘤]