Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak

被引:3
作者
Chatterjee, D
Pantazis, P
Li, G
Bremner, TA
Hendrickson, EA
Wyche, JH
机构
[1] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA
[2] Howard Univ, Dept Biol, Washington, DC 20059 USA
基金
美国国家科学基金会;
关键词
apoptosis; Bak; leukemia cells; differentiation;
D O I
10.1038/sj.onc.1203757
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We demonstrate that treatment of HCW-2 cells, an apoptotic resistant variant of the human HL-60 promyelocytic leukemia cell line with phorbol-12-myristate acetate (PMA), induced differentiation along the monocytic lineage. During this process there was a dramatic increase in the mitochondrial levels of the apoptosis effector, Bail, due to the stabilization of bak mRNA, which was correlated with the sensitization of HCW-2 cells to respond to the apoptotic effect of staurosporine (STS), Treatment of PMA-differentiated, but not undifferentiated, HCW-2 cells induced processing of Bid, substantial efflux of cytochrome c from mitochondria to the cytosol, activation of caspase-3 and apoptosis, The biological significance of the increased mitochondrial Bak in differentiated HCW-2 cells mas supported by the finding that transient transfection of a bak cDNA into HCW-2 cells conferred sensitivity to STS-triggered apoptosis, as determined ba pro-caspase-3 processing, cytochrome c efflux and DNA fragmentation. Our results suggest that the induction of Bak, upon monocytic differentiation, may he a critical event that regulates the apoptotic sensitivity of differentiated HCW-2 cells.
引用
收藏
页码:4108 / 4116
页数:9
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