Suppression of erythroid but not megakaryocytic differentiation of human K562 erythroleukemic cells by Notch-1
Suppression of erythroid but not megakaryocytic differentiation of human K562 erythroleukemic cells by Notch-1
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DOI：
10.1074/jbc.m002866200
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发表时间：
2000-06-30
影响因子：
4.8
通讯作者：
Bresnick, EH
中科院分区：
文献类型：
--
作者：
Lam, LT;Ronchini, C;Bresnick, EH
Notch信号转导通路是一个高度保守的调控系统，控制着多种发育过程。我们建立了一个红白血病细胞模型来研究Notch如何调节细胞命运和红白血病细胞分化。K562和HEL细胞表达Notch-1受体和Notch配体Jagged-1。在K562细胞中稳定表达Notch-1的组成型活性胞内结构域（NIC-1）可抑制红系而不影响巨核细胞的成熟。反义Notch-1的表达诱导自发性红系成熟。NIC-1对红系细胞成熟的抑制不是由于红系细胞分化所必需的转录因子加塔-1和TAL-1的下调。微阵列基因表达分析确定了在红细胞成熟过程中激活的基因，NIC-1破坏了这些基因表达的成熟依赖性变化。这些结果表明，NIC-1改变了K562细胞中的基因表达模式，导致红系成熟阻滞，因此表明Notch信号传导可能控制正常和恶性红系祖细胞的发育潜力。
The Notch signal transduction pathway is a highly conserved regulatory system that controls multiple developmental processes. We have established an erythroleukemia cell model to study how Notch regulates cell fate and erythroleukemic cell differentiation. K562 and HEL cells expressed the Notch-1 receptor and the Notch ligand Jagged-1. The stable expression of the constitutively active intracellular domain of Notch-1 (NIC-1) in K562 cells inhibited erythroid without affecting megakaryocytic maturation. Expression of antisense Notch-1 induced spontaneous erythroid maturation. Suppression of erythroid maturation by NIC-1 did not result from down-regulation of GATA-1 and TAL-1, transcription factors necessary for erythroid differentiation. Microarray gene expression analysis identified genes activated during erythroid maturation, and NIC-1 disrupted the maturation-dependent changes in the expression of these genes. These results show that NIC-1 alters the pattern of gene expression in K562 cells leading to a block in erythroid maturation and therefore suggest that Notch signaling may control the developmental potential of normal and malignant erythroid progenitor cells.