δEF1与雌激素受体-α和他莫昔芬耐药关系的研究  

δEF1 and Resistance to Anti-estrogen Therapy in Breast Cancer

作　　者：罗萍[1] 杨爽[2] 杨朝晖[1] 李媛媛[1] 甄江涛[1] 张承玉[1] 赵振营[3] 

机构地区：[1]天津医学高等专科学校,天津300222 [2]南开大学医学院,天津300071 [3]天津市人民医院药学部,天津300121

出　　处：《南开大学学报（自然科学版）》2016年第4期67-72,共6页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：天津市卫生局科技基金(2013KZ127);天津市卫生局科技基金(2014YK28);国家自然科学基金(81503127)

摘　　要：乳腺癌是常见的女性恶性肿瘤,抗雌激素耐药是成功治疗的一大障碍,雌激素受体(ER)-α的减少或消失是产生抗药性的首要机制.δ晶体蛋白增强因子1(δ-crystallin enhancer factor1,δEF1)是锌指同源结构域转录因子家族中的一员,在乳腺癌等诸多肿瘤中均证实有δEF1的异常表达.采用RT-PCR、Western blotting和细胞免疫荧光技术,分析了在δ晶体蛋白增强因子1(δEF1)功能缺失情况下雌激素受体阳性乳腺癌细胞中雌激素受体(ER)-α表达的变化及组蛋白乙酰化对ER-α的影响.同时采用细胞活力实验证实δEF1通过调控ER-α的表达影响乳腺癌细胞对抗雌激素药物他莫西芬(tamoxifen,TAM)的敏感性.结果表明:δEF1被抑制后,乳腺癌细胞中ER-α的表达水平明显升高(p<0.01),细胞对他莫西芬(TAM)的反应增强,存活率降低(p<0.01);而组蛋白乙酰化可以显著恢复细胞中ER-α的表达(p<0.01).Breast cancer is common female malignant tumor, and anti-estrogen drug resistance may affect successful treatment. Reduction or disappearance of estrogen receptor（ER） –α is the primary mechanism of drug resistance. δ-crystallin enhancer factor1（δEF1） is zinc finger homologous structure domain, a member of transcription factor family, abnormally expressed in breast cancer as well as other tumors. In this study, we aim to detect the function of δEF1 on ER-α expression by doing RT-PCR, WB and IF.We found knockdown of δEF1 significantly increased ER- α expression. Also, δEF1 ＋ valproate（histone deacetylase inhibitor） increased ER- α expression. Indeed, δEF1 knockdown enhanced cells response to TAM, an estrogen receptor antagonist. All these findings helped in understanding the function of δEF1 in breast cancer research and treatment.

关 键 词：shδEF1 ER-Α 抗雌激素耐药 表观遗传 乳腺癌 

分 类 号：R730.2[医药卫生—肿瘤] R739.9[医药卫生—临床医学]