Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells - Role of ERCC1-XPF
Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells - Role of ERCC1-XPF
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DOI：
10.1016/s0006-2952(00)00441-x
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发表时间：
2000-11-01
影响因子：
5.8
通讯作者：
Johnson, SW
中科院分区：
文献类型：
--
作者：
Ferry, KV;Hamilton, TC;Johnson, SW
在A2780/ c系列人卵巢癌模型系统中，一些DNA修复试验表明，铂-DNA加合物去除增加与顺铂耐药有关。在目前的研究中，黑麦提供了进一步的证据，证明这些细胞系的抗性表型部分是由于核苷酸切除修复（NER）的增强。发现顺铂耐药性与紫外线抗性增加有关。Northern blur分析显示，ERCC1的表达增加也与顺铂耐药有关。与亲本A2780细胞相比，在最耐药的细胞系C200中发现了其他几个NER基因的组成性过表达。使用含有位点特异性顺铂加合物的质粒底物来测量顺铂敏感和耐药细胞提取液的核苷酸切除活性。使用这种体外实验，C200细胞提取物比A2780细胞提取物表现出大约3倍的活性，类似于紫外线敏感性的差异。与ERCC1-XPF蛋白互补的A2780提取物的活性增加了约2倍，但对C200提取物的切除影响不大。总的来说，这些结果支持ERCC1-XPF内切酶在顺铂耐药模型中作为NER增加的决定因素的作用。(C) 2000 Elsevier Science Inc.；
Increased platinum-DNA adduct removal has been shown by several DNA repair assays to be associated with cisplatin resistance in the A2780/C-series human ovarian cancer model system. In the present study, rye provide further evidence that the resistance phenotype of these cell lines is due, in part, to enhanced nucleotide excision repair (NER). Cisplatin resistance was found to be associated with increased UV resistance. Northern blur analysis revealed that increased expression of ERCC1 was also associated with cisplatin resistance in this panel. Several other NER genes were found to be constitutively overexpressed in the most resistant cell line, C200, as compared with the parental A2780 cells. A plasmid substrate containing a site-specific cisplatin adduct was used to measure the nucleotide excision activity of cell extracts prepared from cisplatin-sensitive and resistant cells. Using this in vitro assay, extracts prepared from C200 cells exhibited approximately 3-fold more activity than extracts prepared from A2780 cells, similar to the difference in UV sensitivity. Complementation of A2780 extracts with ERCC1-XPF protein resulted in approximately 2-fold increased activity, but had little effect on excision in C200 extracts. Overall, these results support a role for the ERCC1-XPF endonuclease as a determinant of increased NER in this cisplatin resistance model. (C) 2000 Elsevier Science Inc.