羟基脲对人红白血病细胞株中珠蛋白基因表达和细胞分化的影响  

THE ROLE OF HYDROXYUREA IN GLOBIN GENE EXPRESSION AND CELL DIFFERENTIATION OF HUMAN ERYTHROLEUKEMIA CELL LINE

作　　者：桂长云[1] 蒋俶 钱若兰[1] 

机构地区：[1]中国科学院上海细胞生物学研究所,上海200031

出　　处：《实验生物学报》1997年第4期375-382,共8页Acta Biologiae Experimentalis Sinica

摘　　要：人红白血病细胞株(HEL细胞)中珠蛋白基因表达具有自己的特点。即只表达胚胎型的γ-珠蛋白基因而不表达成人型的β-珠蛋白基因。羟基脲(Hydroxyurea)是一种抑制DNA合成的小分子有机化合物。它在临床上被用来治疗地中海贫血和镰刀型贫血。我们的实验结果表明:随羟基脲浓度增加HEL细胞的增殖速度减慢。用常规RT-PCR方法和定量PCR分析证明;用羟基脲诱导HEL细胞后,β-珠蛋白基因表达增加,α-珠蛋白基因表达减少,而γ-珠蛋白基因表达变化不明显。对参与珠蛋白表达的转录因子GATA-1和NF-E2的定量PCR分析发现:这两种转录因子的表达均增加3倍以上。因此,羟基脲可能通过某些信号传递途径促进β-珠蛋白基因表达,从而使HEL细胞趋向终末分化。The HEL cells, a human erythroleu-kemia cell line, express mainly the fetal globin gene and small amount of the embryonic (ε) globin gene, but not the adult (β) globin gene. Hydroxyurea. a small organic compound, has been successfully used to treat sickle cell anemia and β-tha-lessaemia. Our data demonstrated that the growth rate of HEL cell proliferation was inhibited by different doses of hydroxy-urea (from 50μmol/L to 200μmol/L). Using both routine RT-PCR and quantitative PCR analyses, we revealed that the expression of β-globin gene was sharply activated and α-globin gene was almost completely silenced when HEL cells were induced for 3 or 5 days. Meanwhile, γ-globin gene was expressed with no much difference between induced and uninduced HEL cells. We also demonstrated that the expression of GATA-1 and NF-E 2. which were two of the most important transcription factors in erythrocyte development, was activated about 3 folds in the induced cells. We suggested that the induction of GATA-1 and NF-E 2 expression by hy-droxyurea might lead to activation of the adult β-globin gene through some pathways of signal transduction, therefore, hydroxyurea might play a role to induce HEL cells to terminal differentiation.

关 键 词：红白血病 细胞株 珠蛋白基因 羟基脲 白血病 

分 类 号：R733.702[医药卫生—肿瘤]