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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2006-10-16
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pubmed:abstractText |
Among the topoisomerase (topo) II isozymes (alpha and beta), topo IIbeta has been suggested to regulate differentiation. In this study, we examined the role of topo IIbeta in all-trans retinoic acid (ATRA)-induced differentiation of myeloid leukemia cell lines. Inhibition of topo IIbeta activity or downregulation of protein expression enhanced ATRA-induced differentiation/growth arrest and apoptosis. ATRA-induced apoptosis in topo IIbeta-deficient cells involved activation of the caspase cascade and was rescued by ectopic expression of topo IIbeta. Gene expression profiling led to the identification of peroxiredoxin 2 (PRDX2) as a candidate gene that was downregulated in topo IIbeta-deficient cells. Reduced expression of PRDX2 validated at the mRNA and protein level, in topo IIbeta-deficient cells correlated with increased accumulation of reactive oxygen species (ROS) following ATRA-induced differentiation. Overexpression of PRDX2 in topo IIbeta-deficient cells led to reduced accumulation of ROS and partially reversed ATRA-induced apoptosis. These results support a role for topo IIbeta in survival of ATRA-differentiated myeloid leukemia cells. Reduced expression of topo IIbeta induces apoptosis in part by impairing the anti-oxidant capacity of the cell owing to downregulation of PRDX2. Thus, suppression of topo IIbeta and/or PRDX2 levels in myeloid leukemia cells provides a novel approach for improving ATRA-based differentiation therapy.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4,4'-(1,2-dimethyl-1,2-ethanediyl)bi...,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA topoisomerase II beta,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PRDX2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidases,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxiredoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase II Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0887-6924
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pubmed:author |
pubmed-author:BukowskiR MRM,
pubmed-author:ChikamoriKK,
pubmed-author:GanapathiM KMK,
pubmed-author:GanapathiRR,
pubmed-author:GrabowskiD RDR,
pubmed-author:GrozavA GAG,
pubmed-author:GudkovA VAV,
pubmed-author:HillJ EJE,
pubmed-author:RybickiL RLR,
pubmed-author:TanimotoMM,
pubmed-author:VaziriS A JSA,
pubmed-author:WangJJ,
pubmed-author:YenAA,
pubmed-author:ZarkhinEE
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pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1809-18
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16932348-Antineoplastic Agents,
pubmed-meshheading:16932348-Apoptosis,
pubmed-meshheading:16932348-Cell Differentiation,
pubmed-meshheading:16932348-Cell Division,
pubmed-meshheading:16932348-DNA Topoisomerases, Type II,
pubmed-meshheading:16932348-DNA-Binding Proteins,
pubmed-meshheading:16932348-Down-Regulation,
pubmed-meshheading:16932348-Enzyme Inhibitors,
pubmed-meshheading:16932348-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:16932348-Gene Expression Regulation, Leukemic,
pubmed-meshheading:16932348-HL-60 Cells,
pubmed-meshheading:16932348-Heat-Shock Proteins,
pubmed-meshheading:16932348-Humans,
pubmed-meshheading:16932348-Leukemia, Myeloid,
pubmed-meshheading:16932348-Peroxidases,
pubmed-meshheading:16932348-Peroxiredoxins,
pubmed-meshheading:16932348-Piperazines,
pubmed-meshheading:16932348-RNA, Messenger,
pubmed-meshheading:16932348-Reactive Oxygen Species,
pubmed-meshheading:16932348-Signal Transduction,
pubmed-meshheading:16932348-Topoisomerase II Inhibitors,
pubmed-meshheading:16932348-Tretinoin
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pubmed:year |
2006
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pubmed:articleTitle |
Downregulation of topoisomerase IIbeta in myeloid leukemia cell lines leads to activation of apoptosis following all-trans retinoic acid-induced differentiation/growth arrest.
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pubmed:affiliation |
Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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