Alu序列甲基化水平与两种乳腺癌细胞系转移能力高度相关

目的 探讨Alu序列甲基化与乳腺癌转移潜能的关系.方法 用亚硫酸氢盐修饰联合限制性内切酶分析法(combined bisulfite restriction analysis,COBRA)、亚硫酸氢盐修饰结合直接测序法(bisulfite sequencing,BSP)检测两株转移能力不同的乳腺癌细胞系MCF7和MDA-MB-435S中Alu甲基化状态,每个样品挑取10个克隆测序.结果 MCF7和MDA-MB-435S中Alu甲基化水平均明显低于报道的正常人体细胞Alu甲基化水平,但MCF7中Alu的甲基化水平明显高于MDA-MB-435S.同时,Alu甲基化位点在基因组中分布不均匀.结论 乳腺癌的转移潜能可能与Alu序列的去甲基化以及去甲基化位点的分布相关,值得进一步探讨.

Methylation Level of Alu Elements is Closely Associated with Metastasis Ability of Breast Cancer Cell Lines MCF7 and MDA-MB-435S

Objective To determine the relationship between methylation level of Alu elements and breast cancer metastasis.Method COBRA and BSP were employed to detect the methylation level of Alu elements in two breast cancer cell lines (MCF7 and MDA-MB-435S) with significant different metastasis potential. For BSP analysis, ten clones of each sample were analyzed.Result The methylation level of Alu in MDA-MB-435S cells was lower than that in MCF7 cells, although the Alu methylation levels in both MCF7 and MDA-MB-435S cells were lower than those in normal tissue cells reported previously. Moreover, the methylated Alu sequences were non-uniform distributed in the genome.Conclusion Demethylation of Alu elements may be involved in breast cancer metastasis. The correlation between methylation status of Alu and breast cancer metastasis deserves further investigation.