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pubmed:abstractText |
While many common chemotherapeutic drugs and other inducers of DNA-damage result in both NF-kappaB nuclear translocation and DNA-binding, we have previously observed that, depending on the precise stimulus, there is great diversity of the function of NF-kappaB. In particular, we found that treatment of U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet (UV-C) light resulted in a form of NF-kappaB that repressed rather than induced NF-kappaB reporter plasmids and the expression of specific anti-apoptotic genes. Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting topoisomerase II, intercalating with DNA and undergoing redox cycling to produce oxygen free radicals. In this study we have investigated other anthracyclines, doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together with the topoisomerase II inhibitor ICRF-193, which all possess differing characteristics, to determine which of these features is specifically required to induce both NF-kappaB DNA-binding and transcriptional repression in U-2 OS cells.
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pubmed:affiliation |
School of Life Sciences, Division of Gene Regulation and Expression, MSI/WTB, Complex, Dow Street, University of Dundee, Dundee, DD1 5EH, Scotland, UK. k.j.campbell@dundee.ac.uk
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