三氧化二砷诱导人骨髓增生异常综合征细胞株MUTZ-1细胞p15INK4B基因表达的研究  

Arsenic trioxide induced p15INK4B gene expression in myelodysplastic syndrome cell line MUTZ 1

作　　者：佟红艳[1] 林茂芳[1] 

机构地区：[1]浙江大学医学院附属第一医院血液科,杭州310003

出　　处：《中华血液学杂志》2002年第12期638-641,共4页Chinese Journal of Hematology

摘　　要：目的　探讨三氧化二砷 (As2 O3 )去甲基化作用的机制。方法　采用甲基化特异PCR(MSP)检测p15INK4B基因甲基化 ,RT PCR方法检测p15、甲基转移酶 (DNMT) 1、DNMT3A、DNMT3B的表达 ,MTT法检测As2 O3 对MUTZ 1细胞的生长抑制。结果　MUTZ 1细胞有p15INK4B基因甲基化 ,p15基因弱表达 ,As2 O3 作用后p15INK4B基因甲基化程度明显下降 ,p15基因表达增强 ,DNMT3A、DNMT3BmRNA的表达下降并呈浓度依赖性。结论　As2 O3 可能通过抑制甲基转移酶DNMT3A、DNMT3B ,或 (和 )直接对p15INK4B基因去甲基化 ,使p15基因表达上调 ,恢复其活性。Objective To investigate the mechanisms of arsenic trioxide (As 2O 3) induced demethylation. Method Methylation of p15INK4B gene in MUTZ 1 cell was detected by PCR using a methylation specific primer (MSP), the expression of P15,DNA methyltransferase(DNMT)1,DNMT3A and DNMT3B gene by RT PCR, the As 2O 3 induced growth inhibition of MUTZ 1 cell by MTT method. Results P15 gene failed to express in MUTZ 1 cells after methylation. The expression was recovered after the cells exposed to As 2O 3. As 2O 3could significantly down regulate DNMT3A and DNMT3B but not DNMT1 gene on mRNA level in a dose dependent manner. Conclusion As 2O 3 could activate the expression of p15 gene by demethylation or/and by inhibiting DNMT3A and DNMT3B gene.

关 键 词：P15基因甲基化 三氧化二砷 骨髓增生异常综合征 MUTZ-1细胞系 甲基转移酶 

分 类 号：R551.3[医药卫生—血液循环系统疾病]