Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance.

Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance.
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DOI:
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发表时间:
2000-03
期刊:
影响因子:
11.2
通讯作者:
M. Komatsu;T. Sumizawa;Masato Mutoh;Zhe-Sheng Chen;K. Terada;T. Furukawa;Xiaolan Yang;Hui Gao
M. Komatsu;T. Sumizawa;Masato Mutoh;Zhe-Sheng Chen;K. Terada;T. Furukawa;Xiaolan Yang;Hui Gao
中科院分区:
医学1区
文献类型:
--
作者:
M. Komatsu;T. Sumizawa;Masato Mutoh;Zhe-Sheng Chen;K. Terada;T. Furukawa;Xiaolan Yang;Hui Gao

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许多顺铂耐药细胞系中顺铂的积累减少,其中一些细胞系中存在顺铂的主动外排泵,但尚未确定。本研究将铜转运P型ATP酶cDNA(ATP 7 B)转染人表皮样癌KB-3-1细胞。过表达P型ATP酶ATP 7 B的转染子KB/WD细胞系对顺铂(8.9倍)和铜(2.0倍)均具有抗性。顺铂在KB/WD细胞中的蓄积低于在模拟转染的KB/CV细胞中,并且顺铂从KB/WD细胞中的外排比KB/CV细胞中的外排增强。KB/WD细胞对锑、砷酸盐、亚砷酸盐、镉、钴等重金属敏感。ATP 7 B在顺铂耐药的前列腺癌PC-5细胞中过表达,但在亲本PC-3细胞和回复突变的PC-5 R细胞中不表达。ATP 7 B可能参与了某些肿瘤的顺铂耐药。
The accumulation of cisplatin is decreased in many cisplatin-resistant cell lines, and an active efflux pump for cisplatin exists in some of them, but it has not yet been identified. In this study, we transfected the copper-transporting P-type ATPase cDNA (ATP7B) into human epidermoid carcinoma KB-3-1 cells. The transfectant, KB/WD cell line, which overexpressed the P-type ATPase, ATP7B, was resistant to both cisplatin (8.9-fold) and copper (2.0-fold). The accumulation of cisplatin in KB/WD cells was lower than in mock-transfected KB/CV cells, and the efflux of cisplatin from KB/WD cells was enhanced compared with KB/CV cells. KB/WD cells were sensitive to other heavy metals, such as antimony, arsenate, arsenite, cadmium, and cobalt. ATP7B was overexpressed in cisplatin-resistant prostate carcinoma PC-5 cells but not in the parental PC-3 cells and the revertant PC-5R cells. ATP7B may be involved in cisplatin resistance in some tumors.