Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34+ cells by hematopoietic growth factors:: implication of survivin expression in normal hematopoiesis
Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34+ cells by hematopoietic growth factors:: implication of survivin expression in normal hematopoiesis
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DOI：
10.1182/blood.v98.7.2091
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发表时间：
2001-10-01
期刊：
影响因子：
20.3
通讯作者：
Pelus, LM
中科院分区：
文献类型：
--
作者：
Fukuda, S;Pelus, LM
凋亡通道蛋白生存素在大多数癌症和白血病以及胎儿发育过程中表达，但在大多数正常成人组织中不表达。在脐带血（UCB）和成人骨髓CD 34（+）细胞以及因子依赖性MO 7 e细胞系中分析了Survivin表达;还研究了Survivin表达是否受造血生长因子调节。Survivin mRNA和蛋白在新鲜脐血和骨髓CD 34（+）细胞中均有表达。血小板生成素、FIt 3配体和干细胞因子联合使用在24小时内上调了CD 34+细胞中生存素的表达;生存素的表达与细胞周期有关，在G（2）/M期最高，而生长因子的去除导致生存素表达下降。用Hoechst 33342/派洛宁-Y对UCB CD 34（+）进行细胞周期分级显示，存活素信息在新鲜分离的Go细胞中检测不到，但在G1细胞中存在。细胞因子刺激后，在G_0、G_1、CD 34（+）细胞以及进入S期和G_2/M期的细胞中均观察到Survivin mRNA和蛋白的表达，表明Survivin的表达在细胞周期的各个时相都受到调节。这与癌细胞中生存素主要在G（2）/M期间表达形成对比。在CD 34（+）细胞和MO 7 e细胞中，生长因子介导的Survivin上调与凋亡抑制相关，而Survivin下调与凋亡增加一致。此外，在CD 34（+）细胞中观察到Survivin和活性caspase-3之间的负相关。这些发现表明，生存素不是一种癌症特异性抗凋亡蛋白，并在正常成人造血中起着调节作用。(C)2001年，美国血液学会。
The inhibitor-of-apoptosis protein survivin Is expressed in most cancers and leukemias and during fetal development, but not in most normal adult tissues. Survivin expression was analyzed In umbilical cord blood (UCB) and adult bone marrow CD34(+) cells and in the factor-dependent MO7e cell line; also investigated was whether survivin expression was regulated by hematopoietic growth factors. Survivin messsenger RNA (mRNA) and protein were expressed in fresh UCB and marrow CD34(+) cells. The combination of thrombopoietin, FIt3 ligand, and stem cell factor upregulated survivin expression In CD34(+) cells within 24 hours; survivin expression was cell-cycle related and highest during G(2)/M, whereas growth-factor withdrawal resulted in decreased survivin expression. Cell-cycle fractionation of UCB CD34(+) with Hoechst33342/pyronin-Y demonstrated that survivin message was undetectable in freshly isolated Go cells, but present in G, cells. After cytokine stimulation, survivin mRNA and protein expression were observed in both Go and G, CD34(+) cells as well as in cells that had progressed to S and G(2)/M phase, Indicating that survivin expression is regulated in all phases of the cell cycle. This contrasts with the expression of survivin predominantly during G(2)/M in cancer cells. In CD34(+) cells and MO7e cells, growth factor-mediated upregulation of survivin was associated with inhibition of apoptosis, and downregulation of survivin was coincident with increased apoptosis. Furthermore, an inverse correlation between survivin and active caspase-3 was observed in CD34(+) cells. These findings demonstrate that survivin is not a cancer-specific antiapoptotic protein and plays a regulatory role in normal adult hematopoiesis. (C) 2001 by The American Society of Hematology.