Abstract:
:Topoisomerase IIalpha (Topo IIalpha) is an essential nuclear enzyme with a role in the maintenance of DNA topology. Topo IIalpha is a target for several anticancer drugs and the levels of activity of this enzyme have been implicated in the development of drug resistance. Our objective was to identify regulatory transcription factors involved in drug-induced down-regulation of Topo IIalpha. A breast cancer cell line was subjected to a pulsed exposure of doxorubicin and resistant clones propagated. Whole-cell extracts were studied by immunoblotting and RT-PCR for drug-induced changes in the amounts Topo IIalpha, Sp1, Sp3, NF-Y and MDR1. Topo IIalpha levels were reduced in six out of eight cell lines. Of these, three showed concomitant changes in the expression of Sp1 and NF-YA. Thus, we provide the first evidence for roles of Sp1 and NF-Y in bringing about the drug-induced down-regulation of Topo IIalpha gene expression.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Allen KA,Williams AO,Isaacs RJ,Stowell KMdoi
10.1097/00001813-200404000-00008subject
Has Abstractpub_date
2004-04-01 00:00:00pages
357-62issue
4eissn
0959-4973issn
1473-5741pii
00001813-200404000-00008journal_volume
15pub_type
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