alpha-Fetoprotein gene methylation and hepatocarcinogenesis in rats fed a choline-devoid diet.
alpha-Fetoprotein gene methylation and hepatocarcinogenesis in rats fed a choline-devoid diet.
复制标题
缺乏胆碱饮食的大鼠中甲胎蛋白基因甲基化和肝癌发生。
DOI：
10.1093/carcin/8.2.241
复制
发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Lombardi,B
中科院分区：
文献类型：
--
作者：
Locker,J;Hutt,S;Lombardi,B
我们研究了喂食缺乏胆碱或补充胆碱饮食的大鼠肝脏中 DNA 的甲胎蛋白 (AFP) 基因甲基化，以及缺乏胆碱饮食诱发的肝细胞癌。慢性胆碱缺乏会导致肝细胞甲基化水平降低，但不会降低甲基化模式。然而，肿瘤的甲基化模式发生了改变，3' 端的甲基化显着增加，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，DNA 5' 端甲基化水平下降。肿瘤甲基化模式与胎儿肝脏的活性 AFP 基因相似，但肿瘤中 AFP mRNA 的稳态水平没有增加。 3'去甲基化区域是成年肝脏AFP基因失活的特征，但它在肝细胞肿瘤转化的最后阶段消失。甲基化变化不足以激活该基因。
We studied the α-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.