雌激素受体α和β及其变异体在子宫内膜癌组织的表达  

Expression of estrogen receptors α and β and their variants in tumor endometrial tissues

作　　者：桂黎明[1] 魏丽惠[1] 狄春晖[2] 王建六[1] 屠铮[1] 徐明旭[2] 马大龙[2] 

机构地区：[1]北京大学人民医院妇科,北京100044 [2]北京大学疾病基因研究中心

出　　处：《北京大学学报（医学版）》2001年第5期419-423,共5页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金 ( 30 0 0 0 178);高等学校博士学科点专项科研基金资助~~

摘　　要：目的 :比较雌激素受体两种亚型α和 β及其变异体在子宫内膜癌组织的表达 ,验证子宫内膜癌发生的双受体学说 ,为寻找新的有治疗和 /或预防子宫内膜癌的雌激素拮抗剂提供理论依据。方法 :用RT PCR、DNA测序和限制性内切酶酶切鉴定等方法分析子宫内膜癌和正常子宫内膜组织雌激素受体及其变异体mRNA的表达。结果 :(1)与正常子宫内膜组织比较 ,子宫内膜癌组织ERα及其变异体与ERβ的共表达率分别为 34 %和 6 7% ,差异有显著性 ,(P <0 .0 5 ) ;(2 )ERαmRNA在子宫内膜癌组织的相对表达水平为 0 .880± 0 .16 8,ERβmRNA为0 .5 5 3±0 .10 8,差异显著 (P <0 .0 5 ) ;(3)在正常子宫内膜和子宫内膜癌组织中未检测出ERβ变异体。 (4 )野生型 (wild type ,wt)ERαmRNA表达水平较各类△ERαmRNA表达高 (P <0 .0 5或 0 .0 1) ;(5 )ERα变异体的类型包括△ 2ERα单独缺失、△ 4ERα和△ 5ERα的联合缺失、△ 7ERα的单独缺失以及△ 7ERα和部分△ 8ERα的联合缺失 ,在正常子宫内膜和子宫内膜癌组织无区别。结论 :(1)子宫内膜癌的发生受wtERβ和wtERα及其变异体的共调节 ;(2 )子宫内膜癌组织ERα的表达水平明显高于ERβ ,而且ERα有 4种剪接形式 ,推测子宫内膜癌的发生与ERα关系更密切。Objecive: To verify the 'dual receptor hypothesis' of human endometrial tumogenesis and provide theoretical basis for ultimately probing newly therapeutical and preventive antiestrogen for endometrial cancer. Methods: The expression of ERα and ERβ and their variants in both above mentioned tissues was analysed with reverse transcription polymerase chain reaction (RT PCR), DNA sequencing and restriction enzyme analysis. Results: (1) Comparable to normal tissues(34%), a significantly higher proportion(66.7%) of endometrial cancer tissues coexpressed ERα and ERβ mRNA( P < 0.01 ); (2) The relative level(0.880±0.168) of ERα mRNA expression was higher in the cancer tissues versus that of ERβ mRNA(0.553±0.108), statistically significant( P < 0.05 ); (3) ERβ mRNA variants were not found in both tissues; (4) The relative level of wtER mRNA increased significantly compared with that of different △ERα mRNA( P <0.05 or 0.01 ); (5) The ERα mRNA variants included exon 2 deleted?exon 7 deleted, combined exon 4 5 deleted and exon 7 P8 deleted variants, and there were no striking differences in both cancer and normal tissues. Conclusion:(1) The tumogenesis of uterine endometrium was mediated via wtERβ and wtERα and their variants; (2) Our findings suggest that the tumogenesis of endometrial cancer is tightly associated with ERα because the relative level of ERα mRNA expression is higher than that of ERβ, and ERα mRNA includes four different splicing variants.

关 键 词：雌激素 代谢 子宫内膜肿瘤 病理学 雌激素Α受体 雌激素Β受体 

分 类 号：R737.33[医药卫生—肿瘤]