Evidence for a critical role of DNA topoisomerase IIalpha in drug sensitivity revealed by inducible antisense RNA in a human leukaemia cell line.

Abstract:

:To examine the role of human DNA topoisomerase IIalpha (topo IIalpha) in drug resistance, we selectively inhibited topo IIalpha gene expression in U937 human monocytic leukaemia cells stably transfected with a plasmid that allowed for Zn-mediated conditional expression of a human alpha-topo IIalpha antisense sequence. Expression of topo IIalpha mRNA was reduced to <30%, whereas no significant alteration of topo IIbeta mRNA expression was observed. Under these conditions, drug sensitivity to the topo-II-directed agents, etoposide and daunorubicin, was reduced to approximately 50%, whereas sensitivity to 4-hydroperoxy-cyclophosphamide (4-HC) was not altered. This suggests that a reduced amount of topo IIalpha mRNA may be sufficient for the resistance to topo II inhibitors in leukaemia cells.

journal_name

Br J Haematol

authors

Towatari M,Adachi K,Marunouchi T,Saito H

doi

10.1046/j.1365-2141.1998.00713.x

subject

Has Abstract

pub_date

1998-06-01 00:00:00

pages

548-51

issue

3

eissn

0007-1048

issn

1365-2141

journal_volume

101

pub_type

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