Abstract
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.
Highlights
The Notch signal transduction pathway is a highly conserved regulatory system that controls multiple developmental processes [1, 2]
To begin to assess whether Notch signaling regulates erythroid or megakaryocytic differentiation of K562 cells, we asked whether components of the Notch pathway are expressed in these cells
RNA isolated from untreated, hemin-treated, or TPA-treated K562 cells and another human erythroleukemia (HEL) cell line was analyzed by RTPCR with Notch-1, Jagged-1, and HPRT primers
Summary
The Notch signal transduction pathway is a highly conserved regulatory system that controls multiple developmental processes [1, 2]. The stable expression of the constitutively active intracellular domain of Notch-1 (NIC-1) in K562 cells inhibited erythroid without affecting megakaryocytic maturation. These results show that NIC-1 alters the pattern of gene expression in K562 cells leading to a block in erythroid maturation and suggest that Notch signaling may control the developmental potential of normal and malignant erythroid progenitor cells.
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