Document Detail


The differentiating and apoptotic effects of 2-aza-5'-deoxycytidine are dependent on the PU.1 expression level in PU.1-transgenic K562 cells.
MedLine Citation:
PMID:  22459451     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The use of 5-aza-2'-deoxycytidine (5-azadc) for myelodysplastic syndrome, acute myeloid leukemia and chronic myeloid leukemia is becoming an effective and attractive option for these hematological malignancies. The PU.1 transcription factor is important for cellular differentiation through the control of its target genes not only in myeloid and B-lymphoid cells, but also in erythroid cells. Downregulation of PU.1 was reported to play a role in the pathogenesis of various hematological malignancies. In this study, we sought to identify the relationship between the effects of 5-azadc and PU.1. For this purpose, we employed PU.1-knockdown K562 (K562 PU.1KD) cells stably expressing PU.1 short inhibitory RNAs and PU.1-overexpressing K562 (K562 PU.1OE) cells. Therapeutic concentrations (0.1 and 0.5 μM) of 5-azadc resulted in growth arrest in the G2/M phase. Strikingly, however, K562 PU.1OE cells had significantly increased rates of G2/M and apoptotic sub-G1 phase cells. We observed the induction of cyclin B1, a regulator of the G2/M transition, after the addition of 5-azadc. This induction was abolished in K562 PU.1KD cells, but significantly induced in K562 PU.1OE cells. Further analyses revealed potent induction of hemoglobin A1 expression in K562 PU.1OE cells. Taken together, these findings suggest that the PU.1 expression level is tightly related to the differentiating and apoptotic effects of 5-azadc in K562 cells.
Authors:
Sayuri Aoyama; Hiroko Nakano; Mikio Danbara; Masaaki Higashihara; Hideo Harigae; Shinichiro Takahashi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-20
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  420     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-23     Completed Date:  2012-06-22     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  775-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0373, Japan.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Azacitidine / analogs & derivatives*,  pharmacology
Cell Differentiation / drug effects*
Cyclin B1 / metabolism
DNA Damage
Erythroid Cells / cytology,  drug effects*,  metabolism
Gene Expression
Gene Knockdown Techniques
Histones
Humans
K562 Cells
Proto-Oncogene Proteins / biosynthesis*,  genetics
Trans-Activators / biosynthesis*,  genetics
Transgenes
beta-Globins / biosynthesis,  genetics
Chemical
Reg. No./Substance:
0/Cyclin B1; 0/H2AFX protein, human; 0/Histones; 0/Proto-Oncogene Proteins; 0/Trans-Activators; 0/beta-Globins; 0/proto-oncogene protein Spi-1; 320-67-2/Azacitidine; 776B62CQ27/decitabine

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