Locker J, Hutt S, Lombardi B
Carcinogenesis. 1987 Feb;8(2):241-6. doi: 10.1093/carcin/8.2.241.
We studied the alpha-fetoprotein (AFP) gene methylation of DNA from livers of rats fed choline-devoid or control choline-supplemented diets, and from hepatocellular carcinomas induced by the choline-devoid diet. Chronic choline deficiency caused a reduction in the level but not the pattern of methylation in hepatocytes. The tumors, however, had an altered methylation pattern with a marked increase in methylation at the 3' end, even those tumors that had low average DNA methylation. At the same time, there was a decrease in DNA methylation at the 5' end. The tumor methylation pattern resembled that of the active AFP gene of fetal liver but there was no increase in the steady-state level of AFP mRNA in the tumors. The 3' demethylated region is characteristic of the inactive adult liver AFP gene, but it disappears in the final stages of neoplastic transformation of hepatocytes. The methylation changes are not sufficient to activate the gene.
我们研究了喂食缺乏胆碱或补充对照胆碱饮食的大鼠肝脏DNA以及由缺乏胆碱饮食诱导的肝细胞癌中α-甲胎蛋白（AFP）基因的甲基化情况。慢性胆碱缺乏导致肝细胞中甲基化水平降低，但甲基化模式未改变。然而，肿瘤的甲基化模式发生了改变，3'端甲基化显著增加，即使是那些平均DNA甲基化水平较低的肿瘤也是如此。与此同时，5'端的DNA甲基化减少。肿瘤的甲基化模式类似于胎儿肝脏中活跃的AFP基因，但肿瘤中AFP mRNA的稳态水平并未增加。3'去甲基化区域是成年肝脏中不活跃的AFP基因的特征，但在肝细胞肿瘤转化的最后阶段它会消失。甲基化变化不足以激活该基因。
