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

机译:天然和合成类维生素A诱导人早幼粒细胞白血病HL-60细胞分化和细胞毒性的基因表达分析。

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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.
机译:目的:本研究分析了天然和合成类维生素A(ATRA,RII和R9158)处理的人类早幼粒细胞白血病HL-60细胞的基因表达谱,以试图研究类维生素A诱导细胞分化和细胞毒性的结构-功能关系。主要方法:流式细胞仪用于确定天然和合成类维生素A(ATRA,RII和R9158)处理(1.0μM)后HL-60细胞的细胞周期变化,并使用cDNA微阵列监测HL-60基因表达谱。用各种类视黄醇处理60个细胞。主要发现:与类视黄醇诱导的细胞分化一致,用这三种类视黄醇进行治疗与细胞周期G1 / G0期停滞的细胞百分比增加有关。微阵列分析显示,类维生素A处理后,已知的分化基因,粘附分子和氧化酶激活途径上调。在用三种类维生素A处理的HL-60细胞中观察到几种基因的差异表达。例如,组织重塑蛋白基因,泛素基因和信号转导基因在经ATRA和R9158处理的HL-60细胞中高表达,但在经RII处理的HL-60细胞中保持不变。意义:以上发现提示这三种类维生素A诱导HL-60细胞的分化途径相似,并且与类维生素A以及细胞分化和细胞毒性的诱导存在结构-功能关系。

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