Gene expression analysis of human promyelocytic leukemia HL-60 cell differentiation and cytotoxicity induced by natural and synthetic retinoids.

Aims: This study analyzed gene expression profiles of human promyelocytic leukemia HL-60 cells treated with natural and synthetic retinoids (ATRA, RII and R9158), in an attempt to investigate the structure-function relationship of the retinoids in inducing cell differentiation and cytotoxicity.

Main Methods: Flow cytometry was used to determine cell cycle changes in HL-60 cells following treatment (1.0 muM) with natural and synthetic retinoids (ATRA, RII and R9158), and cDNA microarrays were used to monitor the gene expression profiles of HL-60 cells treated with the various retinoids.

Key Findings: Consistent with retinoid-induced cell differentiation, treatment with these three retinoids correlated with an increase in the percentage of cells arrested in the G1/G0 phase of the cell cycle. Microarray analysis showed upregulation of known differentiation genes, adhesion molecules, and the oxidase activation pathway following retinoid treatment. Differential expression of several genes was observed in HL-60 cells treated with the three retinoids. For example, tissue remodeling protein genes, ubiquitin genes, and signal transduction genes were highly expressed in ATRA- and R9158-treated HL-60 cells, but remained unchanged in HL-60 cells treated with RII.

Significance: The above findings suggest that the differentiation of HL-60 cells induced by the three retinoids occurs through similar pathways, and that there exists a structure-function relationship regarding retinoids and the induction of cell differentiation and cytotoxicity.