Notch induces cell cycle arrest and apoptosis in human erythroleukaemic TF-1 cells
Notch induces cell cycle arrest and apoptosis in human erythroleukaemic TF-1 cells
复制标题
DOI：
10.1016/j.bcmd.2008.06.003
复制
发表时间：
2008-11-01
影响因子：
2.3
通讯作者：
Buckle, Anne-Marie
中科院分区：
文献类型：
--
作者：
Chadwick, Nicholas;Fennessy, Carl;Buckle, Anne-Marie
目的：Notch信号通路可以促进造血干细胞的自我更新，并影响祖细胞的谱系承诺决定。本研究旨在探讨Notch诱导红白血病细胞株TF-1和原代脐血CD34+细胞凋亡的机制。方法：构建含有Notch活性形式和Notch信号通路成分的逆转录病毒载体，通过S期标志物Ki67和Annexin V免疫组织化学染色检测其对细胞周期动力学和细胞凋亡的影响。结果：Notch激活后，TF-1细胞发生细胞周期停滞，细胞发生非细胞因子依赖性的凋亡。已知的Notch信号转导靶点Deltex 1、HES1和HERP2对TF-1细胞的转导表明，Notch诱导的细胞周期停滞不是由这些蛋白介导的。然而，对细胞周期基因表达的分析表明，在TF-1细胞和原代脐血CD34+细胞中，Notch信号与IFI16表达上调有关。结论：这些数据表明，在TF-1细胞中，Notch信号可以诱导细胞周期停滞和凋亡。(C)2008 Elsevier Inc.保留所有权利。
Objective: Notch signalling is known to promote hematopoietic stem cell self-renewal and to influence the lineage commitment decisions of progenitor cells. The purpose of this study was to investigate the mechanism of Notch-induced apoptosis in the erythroleukaemic cell line TF-1, and in primary cord blood CD34+ cells.Methods: Retroviral constructs containing constitutively active forms of Notch as well as components of the Notch signalling pathway were used to transduce cells and their effect on cell cycle kinetics and apoptosis assayed by immunostaining for the S-phase marker Ki67 and Annexin V.Results: We found that TF-1 cells undergo cell cycle arrest followed by apoptosis in a cytokine-independent manner in response to active Notch. Transduction of TF-1 cells with known targets of Notch signalling, Deltex1, HES1 and HERP2, showed that Notch-induced cell cycle arrest was not mediated by these proteins. However, analysis of cell cycle gene expression revealed that Notch signalling was associated with an up-regulation of IFI16 expression in TF-1 cells and in primary cord blood CD34+ cells.Conclusion: These data demonstrate that, in the context of TF-1 cells, Notch signalling can induce cell cycle arrest and apoptosis. (C) 2008 Elsevier Inc. All rights reserved.