ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells
ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells
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DOI：
10.1002/1097-0215(20000920)89:5
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发表时间：
2000-09-20
影响因子：
6.4
通讯作者：
Murray, D
中科院分区：
文献类型：
--
作者：
Britten, RA;Liu, D;Murray, D
顺铂是一种有价值的辅助放射治疗宫颈癌。由于顺铂与放疗联合的优势可能归因于这两种药物的细胞杀伤作用，因此此类方案应主要使固有顺铂敏感性肿瘤的患者受益。因此，开发一种快速评估宫颈肿瘤顺铂反应性的分子检测方法将是非常有价值的，我们研究了ERCC 1核苷酸切除修复基因的高治疗前mRNA水平是否可以预测早期传代人宫颈癌细胞中的顺铂耐药性，因为它们在其他几种肿瘤类型中。分别通过北方和蛋白质印迹法在一组对顺铂表现出广泛的固有敏感性的单细胞来源的宫颈癌细胞系中建立ERCC 1基因在mRNA和蛋白质水平上的表达。ERCC 1 mRNA水平与这些细胞系中顺铂耐药性之间的相关性（P小于或等于0.011），然而，ERCC 1蛋白表达水平与顺铂耐药无明显关系。因此，高ERCC 1 mRNA水平与顺铂耐药性之间的相关性可能是一种附带现象，尽管如此，治疗前ERCC 1 mRNA水平可能是识别可能对顺铂难治的宫颈肿瘤的有用分子标志物，并且需要对临床活检材料进行进一步研究。(C)2000 Wiley-Liss，Inc.
Cisplatin is a valuable adjuvant to radiotherapy for the treatment of cervical cancer. Because the advantage of combining cisplatin with radiotherapy is likely to be attributable to additive cell killing by these 2 agents, such protocols should primarily benefit patients who have inherently cisplatin-sensitive tumors. Development of a molecular assay to rapidly evaluate the cisplatin responsiveness of cervical tumors would thus be extremely valuable, We investigated whether high pre-treatment mRNA levels of the ERCC1 nucleotide excision repair gene are predictive of cisplatin resistance in early-passage human cervical cancer cells, as they are in several other tumor types. Expression of the ERCC1 gene at the mRNA and protein levels was established by Northern and Western blotting, respectively, in a panel of single-cell-derived cervical carcinoma cell lines that exhibited a wide range of inherent sensitivity to cisplatin, There was a significant (P less than or equal to 0.011) correlation between ERCC1 mRNA levels and cisplatin resistance in these cell lines, However, there was no obvious relationship between ERCC1 protein levels and cisplatin resistance. Thus, the association between high ERCC1 mRNA levels and cisplatin resistance might be an epiphenomenon, Nonetheless, pre-treatment ERCC1 mRNA levels may be a useful molecular marker for identifying cervical tumors likely to be refractory to cisplatin, and further investigation in clinical biopsy material is warranted. (C) 2000 Wiley-Liss, Inc.