Overexpression of multidrug resistance protein gene in human cancer cell lines selected for drug resistance to epipodophyllotoxins.
Overexpression of either the multidrug resistance 1 (MDR1) gene or multidrug resistance protein (MRP) gene is involved in acquisition of multidrug-resistant phenotypes in human cancer cells. In this study we examined whether selection for resistance to the epipodophyllotoxins, etoposide/teniposide (VP16/VM26), could induce overexpression of MDR1 or MRP. We have previously isolated two VP16/VM26-resistant KB cell lines. Two VP16/VM26-resistant KB cell lines, KB/VM-1 and KB/ VM-4, which were selected by stepwise exposure to VM26 had decreased accumulation of [3H]VP16 and increased levels of MRP, but no apparent expression of MDR1 gene was observed. Another VP16/VM26-resistant KB cell line, KB/VP-4, which was further isolated from a VP16-resistant KB cell line, KB/VP-2, had decreased accumulation of [3H]VP16 and showed overexpression of MRP gene, but not that of MDR1 gene. We also isolated a VP16-resistant cell line, IN157/VP-1, from a human glioma cell line IN157. IN157/VP-1 cells showed decreased accumulation of [3H]VP16 and overexpression of MRP gene, but not of MDR1. These findings suggest that selection for resistance to VP16/VM26, preferentially induces overexpression of MRP gene.
Koike
K
K
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka.
Abe
T
T
Hisano
T
T
Kubo
T
T
Wada
M
M
Kohno
K
K
Kuwano
M
M
D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D005047:Etoposide / Q000493:pharmacokinetics / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D013713:Teniposide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013713:Teniposide