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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 a common malignant tumor in women, anti-estrogen resistance is a major obstacle to successful treatment, the reduction or elimination of estrogen receptor (ER) -α is the primary mechanism of drug resistance.δ-CRP1 δ-crystallin enhancer factor1, δEF1) is a member of the zinc finger homology domain transcription factor family, and abnormal expression of δEF1 was confirmed in many tumors such as breast cancer. RT-PCR, Western blotting and immunofluorescence , The change of estrogen receptor (ER) -α expression in estrogen receptor positive breast cancer cells and the effect of histone acetylation on the expression of ER-α in the absence of δE1 (δEF1) function were analyzed. At the same time, the cell viability assay confirmed that δEF1 affected the sensitivity of breast cancer cells to anti-estrogen tamoxifen (TAM) by regulating the expression of ER-α.The results showed that the expression of ER-α (P <0.01). The response of cells to tamoxifen (TAM) was enhanced and the survival rate was decreased (p <0.01). However, histone acetylation significantly restored the expression of ER-α p <0.01).