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-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.
Komatsu
M
M
Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine, Kagoshima University, Japan.
Sumizawa
T
T
Mutoh
M
M
Chen
Z S
ZS
Terada
K
K
Furukawa
T
T
Yang
X L
XL
Gao
H
H
Miura
N
N
Sugiyama
T
T
Akiyama
S
S
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
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