CREB knockdown inhibits growth and induces apoptosis in human pre-B acute lymphoblastic leukemia cells through inhibition of prosurvival signals

被引:27
作者
Shabestari, Rima Manafi [1 ]
Safa, Majid [1 ,3 ]
Alikarami, Fatemeh [1 ]
Banan, Mehdi [2 ]
Kazemi, Ahmad [1 ]
机构
[1] Iran Univ Med Sci, Fac Allied Med, Dept Hematol, Hemmat Highway, Tehran 1449614535, Iran
[2] Univ Social Welf & Rehabil Sci, Genet Res Ctr, Tehran, Iran
[3] Iran Univ Med Sci, Sch Allied Med Sci, Cellular & Mol Res Ctr, Tehran, Iran
关键词
CREB; BCP-ALL; Apoptosis; Bcl-2; TARGETING SURVIVIN; MCL-1; PHOSPHORYLATION; HEMATOPOIESIS; EXPRESSION; INDUCTION; P53;
D O I
10.1016/j.biopha.2016.12.070
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
A majority of acute lymphoblastic leukemia patients overexpress CREB in the bone marrow. However, the functional significance of this up-regulation and the detailed molecular mechanism behind the regulatory effect of CREB on the growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells has not been elucidated. We demonstrated here that CREB knockdown induced apoptosis and impaired growth of BCP-ALL NALM-6 cells which was associated with caspase activation. The gene expression levels of prosurvival signals Bcl-2 ,Mcl-1, Bcl-xL, survivin and XIAP were down-regulated upon CREB suppression. These findings indicate a critical role for CREB in proliferation, survival, and apoptosis of BCP-ALL cells. The data also suggest that CREB could possibly serve as potential therapeutic target in BCP-ALL. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:274 / 279
页数:6
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