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ID 11518
Eprint ID
11518
FullText URL
Thumnail O004168.pdf 92.9 KB
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
Author
Chikamori, Ken-ichi
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.
Keywords
retinoids
differentiation
topoisomerase IIbeta
apoptosis
myeloid leukemia
peroxiredoxin 2
Note
http://dx.doi.org/10.1038/sj.leu.2404351
Published Date
2007-03-23
Publication Title
Content Type
Thesis or Dissertation
Grant Number
乙第4168号
Granted Date
2007-03-23
Thesis Type
博士(医学)
Grantor
岡山大学
Official Url
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16932348&dopt=Abstract
language
日本語
File Version
none
Refereed
Unknown