ID | 11518 |
Eprint ID | 11518
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FullText URL | |
Title Alternative | トポイソメラーゼIIβの発現抑制は骨髄性白血病細胞株においてオールトランスレチノイン酸(ATRA)による分化誘導あるいは増殖停止に引き続いてアポトーシスを誘導する
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Author |
Chikamori, Ken-ichi
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Abstract | 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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Keywords | retinoids
differentiation
topoisomerase IIbeta
apoptosis
myeloid leukemia
peroxiredoxin 2
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Note | http://dx.doi.org/10.1038/sj.leu.2404351
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Published Date | 2007-03-23
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Publication Title | |
Content Type |
Thesis or Dissertation
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Grant Number | 乙第4168号
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Granted Date | 2007-03-23
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Thesis Type |
Doctor of Philosophy in Medical Science
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Grantor | 岡山大学
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Official Url | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16932348&dopt=Abstract
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language |
Japanese
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File Version | none
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Refereed |
Unknown
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