Sun Yehong, Li Tiyuan, Ma Kewei, Tian Zhongkai, Zhu Ying, Chen Fuqiang, Hu Gang
Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Cancer Invest. 2009 Nov;27(9):891-7. doi: 10.3109/07357900902744536.
Excision repair cross complementation group-1 (ERCC1) was reported to be responsible for drug resistance during cancer treatment. In this report, we first proved the existence of ERCC1 exon VIII alternative splicing in ovarian cancer cells. Further investigation showed that over-expressed exon VIII deficient ERCC1 variant failed to change the protein level of ERCC1 in cancer cells, but decreased the excision repair function of ERCC1 and enhanced sensitivity of cancer cells to cisplatin in a dose-dependent manner. The results indicate that ERCC1 exon VIII alternative splicing does exist in some ovarian cancer cell lines, and regulates cisplatin-resistance in ovarian cancer cells.
据报道,切除修复交叉互补组1(ERCC1)在癌症治疗期间与耐药性有关。在本报告中,我们首次证实卵巢癌细胞中存在ERCC1外显子VIII可变剪接。进一步研究表明,过表达的外显子VIII缺陷型ERCC1变体未能改变癌细胞中ERCC1的蛋白水平,但降低了ERCC1的切除修复功能,并以剂量依赖的方式增强了癌细胞对顺铂的敏感性。结果表明,ERCC1外显子VIII可变剪接确实存在于某些卵巢癌细胞系中,并调节卵巢癌细胞的顺铂耐药性。