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ID 11518
Eprint ID
11518
フルテキストURL
Thumnail O004168.pdf 92.9 KB
タイトル(別表記)
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
著者
近森 研一 岡山大学
抄録
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.
キーワード
retinoids
differentiation
topoisomerase IIbeta
apoptosis
myeloid leukemia
peroxiredoxin 2
備考
http://dx.doi.org/10.1038/sj.leu.2404351
発行日
2007-03-23
出版物タイトル
資料タイプ
学位論文
学位授与番号
乙第4168号
学位授与年月日
2007-03-23
学位・専攻分野
博士(医学)
授与大学
岡山大学
オフィシャル URL
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16932348&dopt=Abstract
言語
Japanese
論文のバージョン
none
査読
不明