Molecular mechanism of granulocytic differentiation of human promyelocytic leukemia HL-60 cells induced by all-trans retinoic acid.

Yao Xue Xue Bao

Applied Research Center for Genomic Technology, Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, China.

Published: January 2004

Aim: To elucidate the molecular mechanism of granulocytic differentiation of human promyelocytic leukemia HL-60 cells induced by all-trans-retinoic acid (ATRA).

Methods: Flow cytometry was used to determine the cell cycle changes of HL-60 cells upon ATRA treatment. Gene expression profiles of HL-60 cells induced by 1 mumol.L-1 ATRA were obtained by using cDNA microarrays containing 9,984 genes and expressed sequence tags (ESTs).

Results: Cell cycle analysis showed that 48%-73% of cells were arrested at G1/G0 phase upon ATRA treatment; cDNA microarray results demonstrated that the expression of genes encoding adhesion molecules, tissue remodeling proteins, transporters and ribosomal proteins were up-regulated in ATRA treated of HL-60 cells. Several genes involved in oxidase activation pathway were also differentially expressed.

Conclusion: ATRA treatment induced growth arrest and differentiation in HL-60 cells, which is associated with regulation of the oxidase activation pathway and the expression of tissue remodeling proteins.

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