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

Citation
M. Kobayashi et al., Decreased topoisomerase II alpha expression confers increased resistance to ICRF-193 as well as VP-16 in mouse embryonic stem cells, CANCER LETT, 166(1), 2001, pp. 71-77
Citations number
21
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER LETTERS
ISSN journal
03043835 → ACNP
Volume
166
Issue
1
Year of publication
2001
Pages
71 - 77
Database
ISI
SICI code
0304-3835(20010510)166:1<71:DTIAEC>2.0.ZU;2-Y
Abstract
To elucidate the relationship between topoisomerase (topo) II expression an d 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 a n increased resistance to ICRF-193 as well as VP-16, suggesting that ICRF-1 93, like VP-16, exerts its cytotoxicity through converting topo II to a poi son. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.