HSPB8 is methylated in hematopoietic malignancies and overexpression of HSPB8 exhibits antileukemia effect

被引:15
作者
Cui, Xue-Ying [1 ]
Wang, Nan [1 ]
Yang, Bin-Xia [1 ]
Gao, Wei-Feng [1 ]
Lin, Yong-Min [1 ]
Yao, Xing-Rong [1 ]
Ma, Xiao-Tong [1 ]
机构
[1] Chinese Acad Med Sci, Inst Hematol, Peking Union Med Coll, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China
基金
中国国家自然科学基金;
关键词
HEAT-SHOCK-PROTEIN; DNA METHYLATION; 5-AZA-2'-DEOXYCYTIDINE DECITABINE; HSP22; HSPB8; IN-VIVO; CELLS; GENE; H11; EXPRESSION; KINASE;
D O I
10.1016/j.exphem.2011.09.004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
HSPB8 has been shown to be involved in regulation of cell proliferation and apoptosis, and it has also been found to have divergent properties in solid tumors. The purpose of this study was to investigate the expression and function of HSPB8 in hematopoietic malignancies. Expression and induced expression of HSPB8 was evaluated in hematopoietic tumor cell lines and bone marrow samples from patients with leukemia. Methylation status was investigated by methylation-specific polymerase chain reaction. The role of HSPB8 in hematopoietic malignancies was addressed by reintroducing HSPB8 expression into the K562 (leukemia) and Namalwa (lymphoma) cell lines. Expression of HSPB8 was absent in hematopoietic tumor cell lines and primary patient and normal volunteer samples. Promoter DNA methylation of HSPB8 was observed in these cells. HSPB8 expression could be restored after demethylation treatment with 5-aza-2'-deoxycytidine. Overexpression of HSPB8 reduced colony formation of both K562 and Namalwa cell lines, inhibited the cell growth of Namalwa in vitro, and suppressed tumor formation of K562 cells in vivo. The present study demonstrates that HSPB8 is silenced by DNA methylation in hematopoietic malignant and normal cells and its expression can be induced by treatment with 5-aza-2'-deoxycytidine. Overexpression of HSPB8 may have an antitumor activity in chronic myelogenous leukemia and lymphoma. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
引用
收藏
页码:14 / 21
页数:8
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