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睾丸肿瘤细胞系中XPA、ERCC1和XPF DNA修复蛋白水平降低。

Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines.

作者信息

Welsh Carey, Day Roger, McGurk Claire, Masters John R W, Wood Richard D, Köberle Beate

机构信息

University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213-1863, USA.

出版信息

Int J Cancer. 2004 Jun 20;110(3):352-61. doi: 10.1002/ijc.20134.

DOI:10.1002/ijc.20134
PMID:15095299
Abstract

Over 80% of patients with advanced metastatic testis tumors can be cured using cisplatin-based combination chemotherapy. This is unusual as metastatic cancer in adults is usually incurable. Cell lines derived from testis tumors retain sensitivity to cisplatin in vitro. We previously investigated 2 testis tumor cell lines with a low capacity to remove cisplatin-induced DNA damage and found that they had low levels of the DNA nucleotide excision repair proteins XPA, ERCC1 and XPF. To determine whether low levels of XPA, ERCC1 and XPF proteins are characteristic of testis tumor cell lines, we investigated 35 cell lines derived from cancers to determine whether groups of cell lines from diverse tissue origins differ from one another in constitutive levels of these NER proteins. Quantitative immunoblotting was used to compare groups of cell lines representing prostate, bladder, breast, lung, cervical, ovarian and testis cancers. Only the 6 testis tumor cell lines showed significantly lower mean levels of XPA (p = 0.001), XPF (p = 0.001) and ERCC1 (p = 0.004) proteins from the other groups. Our results encourage further investigation of the possibility that low levels of these nucleotide excision repair proteins could be related to the favorable response of testis tumors to cisplatin-based chemotherapy.

摘要

超过80%的晚期转移性睾丸肿瘤患者使用基于顺铂的联合化疗可以治愈。这很不寻常,因为成人转移性癌症通常无法治愈。源自睾丸肿瘤的细胞系在体外对顺铂保持敏感。我们之前研究了2个清除顺铂诱导的DNA损伤能力较低的睾丸肿瘤细胞系,发现它们的DNA核苷酸切除修复蛋白XPA、ERCC1和XPF水平较低。为了确定XPA、ERCC1和XPF蛋白水平低是否是睾丸肿瘤细胞系的特征,我们研究了35个源自癌症的细胞系,以确定来自不同组织起源的细胞系组在这些核苷酸切除修复(NER)蛋白的组成水平上是否彼此不同。使用定量免疫印迹法比较代表前列腺癌、膀胱癌、乳腺癌、肺癌、宫颈癌、卵巢癌和睾丸癌的细胞系组。只有6个睾丸肿瘤细胞系的XPA(p = 0.001)、XPF(p = 0.001)和ERCC1(p = 0.004)蛋白平均水平显著低于其他组。我们的结果鼓励进一步研究这些核苷酸切除修复蛋白水平低是否可能与睾丸肿瘤对基于顺铂的化疗的良好反应有关。

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