Barletta J M, Rainier S, Feinberg A P
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cancer Res. 1997 Jan 1;57(1):48-50.
To determine whether loss of imprinting in cancer might be reversed by altering DNA methylation, we treated tumor cells with 5-aza-2'-deoxycytidine, a specific inhibitor of cytosine DNA methyltransferase. Treated cells showed several significant and reproducible changes. (a) Equal expression of maternal and paternal alleles of insulin-like growth factor 2 switched to predominant expression of a single parental allele. (b) H19 expression was reactivated. (c) Biallelic H19 expression switched to monoallelic expression. (d) Biallelic methylation of H19 switched to preferential allelic methylation. These results imply that abnormally imprinted cells are susceptible to epigenetic modification and that the effect of 5-aza-2'-deoxycytidine on tumor cells with loss of imprinting is not random but specific to one allele.
为了确定癌症中的印记丢失是否可以通过改变DNA甲基化来逆转，我们用5-氮杂-2'-脱氧胞苷（一种胞嘧啶DNA甲基转移酶的特异性抑制剂）处理肿瘤细胞。处理后的细胞显示出几个显著且可重复的变化。（a）胰岛素样生长因子2的母本和父本等位基因的平等表达转变为单个亲本等位基因的优势表达。（b）H19表达被重新激活。（c）H19的双等位基因表达转变为单等位基因表达。（d）H19的双等位基因甲基化转变为优先的等位基因甲基化。这些结果表明，异常印记的细胞易受表观遗传修饰的影响，并且5-氮杂-2'-脱氧胞苷对印记丢失的肿瘤细胞的作用不是随机的，而是特定于一个等位基因的。
