Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance
M Komatsu, T Sumizawa, M Mutoh, ZS Chen, K Terada… - Cancer research, 2000 - AACR
M Komatsu, T Sumizawa, M Mutoh, ZS Chen, K Terada, T Furukawa, XL Yang, H Gao…
Cancer research, 2000•AACRThe 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 …
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 …
Abstract
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.
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