title: Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance.
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.
authors.affiliation: Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine, Kagoshima University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Komatsu
authors.forename: T
authors.initials: T
authors.lastname: Sumizawa
authors.forename: M
authors.initials: M
authors.lastname: Mutoh
authors.forename: Z S
authors.initials: ZS
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Terada
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: X L
authors.initials: XL
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.forename: N
authors.initials: N
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: S
authors.initials: S
authors.lastname: Akiyama
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002945:Cisplatin / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D000073840:Copper-Transporting ATPases; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002945:Cisplatin