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

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-t ransporting 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 e nhanced compared with KB/CV cells, KB/WD cells were sensitive to other heav y 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.