Suppression of erythroid but not megakaryocytic differentiation of human K562 Erythroleukemic cells by Notch-1

Lloyd T. Lam, Chiara Ronchini, Jason Norton, Anthony J Capobianco, Emery H. Bresnick

Research output: Contribution to journalArticle

77 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)19676-19684
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number26
DOIs
StatePublished - Jun 30 2000
Externally publishedYes

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K562 Cells
Gene expression
Genes
Notch Receptors
Gene Expression
Signal transduction
Microarrays
Leukemia, Erythroblastic, Acute
Erythroid Precursor Cells
Transcription Factors
Ligands
Control systems
Cell Differentiation
Signal Transduction
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Suppression of erythroid but not megakaryocytic differentiation of human K562 Erythroleukemic cells by Notch-1. / Lam, Lloyd T.; Ronchini, Chiara; Norton, Jason; Capobianco, Anthony J; Bresnick, Emery H.

In: Journal of Biological Chemistry, Vol. 275, No. 26, 30.06.2000, p. 19676-19684.

Research output: Contribution to journalArticle

Lam, Lloyd T. ; Ronchini, Chiara ; Norton, Jason ; Capobianco, Anthony J ; Bresnick, Emery H. / Suppression of erythroid but not megakaryocytic differentiation of human K562 Erythroleukemic cells by Notch-1. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 26. pp. 19676-19684.
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