全反式维甲酸诱导人急性早幼粒白血病HL-60细胞分化的机制(英文)

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

目的 研究全反式维甲酸诱导人急性早幼粒白血病HL 6 0细胞分化机制。方法 用流式细胞仪分析维甲酸对HL 6 0细胞周期变化的影响 ,用自制的含 9984个已知基因和EST的高密度基因芯片检测HL 6 0细胞在维甲酸诱导作用下不同时期的基因表达变化。结果 HL 6 0细胞在 1μmol·L- 1 维甲酸持续作用 2 ,4和 6d时 ,流式细胞仪结果显示 4 8%～ 73%细胞阻断在G0 G1 期 ;基因表达谱分析发现 ,黏附分子、组织重建蛋白、转运蛋白、核蛋白体蛋白和涉及氧化酶激活途径的基因表达明显升高。结论 基因表达谱的研究结果表明 ,维甲酸作用HL 6 0细胞与氧化酶激活途径及组织重建蛋白的表达相关联 ,并揭示了一些已知和未知功能的基因在HL 6 0细胞分化与细胞凋亡过程中的作用。

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 μmol·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 G 1/G 0 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.