Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma
Biallelic expression of the H19 and IGF2 genes in hepatocellular carcinoma
复制标题
DOI：
10.1016/s0304-3835(97)00264-4
复制
发表时间：
1997-11-11
期刊：
影响因子：
9.7
通讯作者：
Lee, YI
中科院分区：
文献类型：
--
作者：
Kim, KS;Lee, YI
印迹基因H19和胰岛素样生长因子II（IGF 2）已被证明是人类胚胎发育所必需的。这两个基因都是双印记的，表达母本H19和父本IGF 2等位基因，并且通常以单等位基因表达为特征。最近，已经在儿童期肿瘤（包括Wilms肿瘤（WT）、胚胎性横纹肌肉瘤）和成年期肿瘤（如肺癌）中观察到这些产生双等位基因表达的基因的印记丧失。为了检测肝癌中是否存在印迹缺失，我们分别用H19和IGF 2基因的ApaI和ApaI多态性分析了3个独立肿瘤、3个肝癌细胞系和1个肝母细胞瘤细胞系中H19和IGF 2基因的印迹状态。与以往报道相比，除1个肿瘤和1个肝癌细胞系外，所有病例均显示H19和IGF 2基因的双等位基因表达。与WT不同，HCC中IGF 2的印迹丢失（LOI）与H19表达的下调无关，而是与H19和IGF 2的共表达相关。因此，在具有LOI的肿瘤中，H19和IGF 2的表达可以解偶联。H19和IGF 2在肝癌中频繁的双等位基因表达可能在肿瘤发生和/或过程中的表观遗传机制中发挥因果作用。(C)1997 Elsevier Science爱尔兰有限公司
The imprinted genes, H19 and insulin like growth factor II (IGF2), have been demonstrated to be necessary for embryonal development in humans. Both genes are reciprocally imprinted, with expression of the maternal H19 and paternal IGF2 alleles, and are normally characterized by monoallelic expression. Recently, loss of imprinting of these genes producing biallelic expression has been observed in childhood tumors including Wilms' tumors (WT), embryonal rhabdomyosarcoma, and adulthood tumors such as lung cancer. To test the existence of loss of imprinting in hepatocellular carcinoma (HCC), we analyzed the status of imprinting of H19 and IGF2 genes in three independent tumors, three HCC and one hepatoblastoma cell lines using AluI and ApaI polymorphisms of these genes, respectively, In contrast to the previous report, all the cases except one tumor and one HCC cell line showed biallelic expression of both H19 and IGF2 genes. Unlike WT, loss of imprinting (LOI) of IGF2 in HCC was not linked to down-regulation of H19 expression, but rather associated with coexpression for H19 and IGF2, Thus, H19 and IGF2 expression can be uncoupled in tumors with LOI. The frequent biallelic expression of H19 and IGF2 in hepatocellular carcinoma might play a causal role in the epigenetic mechanism involved in tumor development and/or process. (C) 1997 Elsevier Science Ireland Ltd.