Shen Jian-Zhen, Xu Cheng-Bo, Fu Hai-Ying, Wu Dang-Sen, Zhou Hua-Rong, Fan Li-Ping
Department of Hematology, Union Hospital of Fujian Medical University, Fujian Institute of Hematology, Fuzhou, China.
Asian Pac J Cancer Prev. 2011;12(10):2617-21.
DNA methylation of CpG islands within the promoters of specific genes may play roles in tumor initiation and progression. It has been suggested such events may serve as critical check points.
The present study analyzed the methylation status of CpG islands within the promoters of secreted frizzled-related proteins (SFRPs) in 87 acute leukemia (AL) patients, 20 normal controls, and four AL cell lines. 5-aza-2'- deoxycytidine (5-Aza-CdR), an inhibitor of DNA methylation, was employed to determine its effect on SFRP expression.
Methylation of at least one SFRP promoter was observed in 69% of the AL patients analyzed. In addition, methylation of all four SFRP promoters was observed in Molt-4, Jurkat, HL60 and NB4 cells. In Jurkat cells, methylation levels of four SFRP promoters decreased in a dose-dependent manner upon treatment with 5-Aza-CdR, which coincided with increased mRNA expression. With increasing 5-Aza-CdR concentrations, the expression of DNA methyltransferases, DNMT3A and DNMT3B, significantly decreased in a dose-dependent manner.
The present study demonstrated that SFRP gene methylation may be involved in AL progression, with a possible epigenetic mechanism influencing Wnt signaling.
特定基因启动子内CpG岛的DNA甲基化可能在肿瘤的发生和发展中起作用。有人提出这些事件可能是关键的检查点。
本研究分析了87例急性白血病（AL）患者、20例正常对照者以及4种AL细胞系中分泌型卷曲相关蛋白（SFRP）启动子内CpG岛的甲基化状态。使用DNA甲基化抑制剂5-氮杂-2'-脱氧胞苷（5-Aza-CdR）来确定其对SFRP表达的影响。
在所分析的AL患者中，69%观察到至少一个SFRP启动子发生甲基化。此外，在Molt-4、Jurkat、HL60和NB4细胞中观察到所有四个SFRP启动子均发生甲基化。在Jurkat细胞中，用5-Aza-CdR处理后，四个SFRP启动子的甲基化水平呈剂量依赖性降低，这与mRNA表达增加相一致。随着5-Aza-CdR浓度的增加，DNA甲基转移酶DNMT3A和DNMT3B的表达呈剂量依赖性显著降低。
本研究表明，SFRP基因甲基化可能参与AL的进展，可能存在一种表观遗传机制影响Wnt信号通路。
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