雌激素通过FTO基因调控子宫内膜癌细胞的增殖活性  

Estrogen regulates cell proliferation by FTO gene

作　　者：周冬梅[1] 廖虹[2] 魏桠楠[1] 吴凌[1] 祝颖[1] 冯怡雯[1] 董金华[1] 董玲玲[2] 席晓薇[1] 张箴波[1,3] 丰有吉[1] 

机构地区：[1]上海交通大学附属第一人民医院妇产科,上海200080 [2]上海同济大学附属第一妇婴保健院 [3]复旦大学附属妇产科医院

出　　处：《现代妇产科进展》2011年第8期600-603,609,共5页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金项目(No:81001155;No:81020108027);上海市卫生局项目(No:2009028)

摘　　要：目的:探讨雌激素对子宫内膜癌细胞系ishikawa细胞中肥胖相关基因FTO表达的调控机制以及对增殖的影响。方法:RT-PCR及细胞免疫荧光法检测不同浓度雌激素处理后ishikawa细胞中FTO表达水平的变化,PCR方法检测雌激素是否通过PI3K/AKT和MAPK信号通路对FTO进行调控,应用siRNA干扰法和MTT分析法检测FTO基因对细胞增殖的影响。结果:(1)不同浓度雌激素均可上调ishkawa细胞中FTO mRNA的表达,以10-9mol/L作用最明显,与对照组的差异有统计学意义(P<0.05);(2)E2+LY294002、E2+U0126组FTO mRNA表达水平比单独加雌激素组显著降低,差异有统计学意义(P<0.05),E2+LY294002+U0126联合加通路抑制剂组比E2+LY294002、E2+U0126单独加通路抑制剂组明显降低,差异有统计学意义(P<0.05);(3)siFTO干扰组FTO mRNA表达水平比阴性对照组明显降低,干扰效率达40%(P<0.05),FTO被干扰后,细胞的增殖活性受到明显的抑制,差异有统计学意义(P<0.05)。结论:雌激素通过受PI3K/AKT和MAPK信号通路调控的FTO基因调控细胞的增殖活性。Objective：To investigate the role of estrogen in regulating FTO gene expression and cell proliferation in human endometrial carcinoma cell.Methods：RT-PCR and immunofluorescence assay expression levels of FTO in ishikawa cells after treatment with different concentrations of estrogen;PCR was used to detect whether estrogen regulates the expression of FTO through the PI3K/AKT and MAPK signal pathways;SiRNA was used to konck down FTO gene and MTT assay was used to determine cellular growth.Result：（1）The FTO mRNA expression can be up-regulated by 17-β E2 in Ishikawa cells.And the effect of 17-β E2 was more obvious at concentrations of 10-9mo1/L（P0.05）.（2）The expression level of FTO mRNA was downregulated by LY294002 and U0126 compared with control group（P0.05）.（3）Inhibition of FTO by RNA interference reduced cell proliferation in Ishikawa cells（P0.05）.Conclusion：Estrogen regulates cell proliferation by FTO gene,and the PI3K/AKT and MAPK pathway was a signal transduction pathway upstream of FTO.

关 键 词：子宫内膜癌 雌激素 FTO SIRNA 

分 类 号：R737.33[医药卫生—肿瘤]