Functional evidence for Eme1 as a marker of cisplatin resistance
Functional evidence for Eme1 as a marker of cisplatin resistance
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DOI：
10.1002/ijc.24268
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发表时间：
2009-06-15
影响因子：
6.4
通讯作者：
Miyagawa, Kiyoshi
中科院分区：
文献类型：
--
作者：
Tomoda, Yoshitaka;Katsura, Mari;Miyagawa, Kiyoshi
预测肿瘤中顺铂敏感性的能力有望大大改善癌症治疗的结果，因为该药物经常用于各种肿瘤。尽管ERCC1和其他修复蛋白已被门控作为顺铂耐药的标志物，但仍然需要可靠的标志物。在这里，我们证明，Eme1水平可以预测顺铂的敏感性更准确地比ERCC1或Rad51在各种人类癌细胞系的水平。Eme1与Mus81形成异二聚体蛋白复合物，并作为结构特异性内切核酸酶发挥作用。Eme1单倍不足导致结肠癌细胞系HCT 116对顺铂的超敏反应。在这一发现的基础上，我们研究了多种来源的人类肿瘤细胞系中参与修复链间交联的蛋白质水平与顺铂敏感性之间的关系。尽管ERCC1、Rad51和Mus81水平在一定程度上与敏感性相关，但观察到与Eme1的相关性最明显。Eme1水平低的肿瘤对药物比水平高的肿瘤更敏感。这表明，肿瘤中Eme1的测量可能对基于顺铂的化疗提供更多信息
The ability to predict cisplatin sensitivity in tumors has been expected to greatly improve the outcome of cancer therapy because the drug is frequently used in a variety of tumors. Although ERCC1 and other repair proteins have be gated as markers of cisplatin resistance, reliable markers are still needed. Here, we demonstrate that Eme1 levels can predict cisplatin sensitivity more accurately than ERCC1 or Rad51 levels in a variety of human cancer cell lines. Eme1 forms a heterodimeric protein complex with Mus81 and functions as a structure-specific endonuclease. Haploinsufficiency of Eme1 led to hypersensitivity to cisplatin in the colon cancer cell line HCT116. On the basis of this finding, we examined the relationships between levels of proteins involved in the repair of interstrand cross-links and cisplatin sensitivity in human tumor cell lines with a variety of origins. Although ERCC1, Rad51 and Mus81 levels correlated with sensitivity to some extent, the clearest correlation was observed with Eme1. Tumors with low Eme1 levels were more sensitive to the drug than tumors with high levels. This suggests that the measurement of Eme1 in tumors may be more informative for cisplatin-based chemotherapy