OVEREXPRESSION OF METALLOTHIONEIN CONFERS RESISTANCE TO ANTICANCER DRUGS
OVEREXPRESSION OF METALLOTHIONEIN CONFERS RESISTANCE TO ANTICANCER DRUGS
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DOI：
10.1126/science.3175622
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发表时间：
1988-09-30
期刊：
影响因子：
56.9
通讯作者：
LAZO, JS
中科院分区：
文献类型：
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作者：
KELLEY, SL;BASU, A;LAZO, JS
对化疗药物的耐药性是癌症治愈性治疗的主要障碍。肿瘤细胞系获得性耐药顺二氨二氯铂（II）过度表达金属硫蛋白，并表现出交叉耐药性烷化剂，如苯丁酸氮芥和美法仑。由于长期暴露于重金属而保持高水平金属硫蛋白的人类癌细胞对顺式二氨二氯铂（II）、美法仑和苯丁酸氮芥具有耐药性。此外，用牛乳头瘤病毒表达载体转染的细胞含有编码人金属硫蛋白-IIA的DNA，对顺二氨二氯铂（II）、美法仑和苯丁酸氮芥耐药，但对5-氟尿嘧啶或长春新碱不耐药。因此，金属硫蛋白的过度表达代表了对临床上重要的抗癌药物的一个子集的耐药机制。
Resistance to antineoplastic agents is the major obstacle to curative therapy of cancer. Tumor cell lines with acquired resistance to the antineoplastic agentcis-diamminedichloroplatinum(II) overexpressed metallothionein and demonstrated cross-resistance to alkylating agents such as chlorambucil and melphalan. Human carcinoma cells that maintained high levels of metallothionein because of chronic exposure to heavy metals were resistant tocis-diamminedichloroplatinum(II), melphalan, and chlorambucil. Furthermore, cells transfected with bovine papilloma virus expression vectors containing DNA encoding human metallothionein-IIAwere resistant tocis-diamminedichloroplatinum(II), melphalan, and chlorambucil but not to 5-fluorouracil or vincristine. Thus, overexpression of metallothionein represents one mechanism of resistance to a subset of clinically important anticancer drugs.