Decreased topoisomerase IIα expression confers increased resistance to ICRF-193 as well as VP-16 in mouse embryonic stem cells

被引：24

作者：

Kobayashi, M

Adachi, N

Aratani, Y

Kikuchi, A

Koyama, H

机构：

[1] Yokohama City Univ, Kihara Inst Biol Res, Totsuka Ku, Yokohama, Kanagawa 2440813, Japan

[2] Yokohama City Univ, Grad Sch Integrated Sci, Totsuka Ku, Yokohama, Kanagawa 2440813, Japan

[3] Nagoya Univ, Sch Med, Dis Mechanism & Control Res Inst, Lab Med Mycol,Showa Ku, Nagoya, Aichi 4668550, Japan

来源：

CANCER LETTERS | 2001年 / 166卷 / 01期

关键词：

topoisomerase II; embryonic stem cell; gene targeting; drug resistance; topoisomerase II inhibitor;

D O I：

10.1016/S0304-3835(01)00447-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To elucidate the relationship between topoisomerase (topo) II expression and sensitivity to anti-topo II drugs in mammalian cells, we generated mouse embryonic stem cell mutants heterozygous for the lope II alpha gene by gene targeting. The level of topo II alpha in the heterozygous cells reduced to one-half of that found in wild-type cells, while topo II beta levels were similar in both cell types. Importantly, the heterozygous cells exhibited an increased resistance to ICRF-193 as well as VP-16, suggesting that ICRF-193, like VP-16, exerts its cytotoxicity through converting topo II to a poison. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：71 / 77

页数：7

共 21 条

[1] MUTANT ISOLATION OF MOUSE DNA TOPOISOMERASE II-ALPHA IN YEAST [J].