ACTIVATION OF C-MYC BY WOODCHUCK HEPATITIS-VIRUS INSERTION IN HEPATOCELLULAR-CARCINOMA
ACTIVATION OF C-MYC BY WOODCHUCK HEPATITIS-VIRUS INSERTION IN HEPATOCELLULAR-CARCINOMA
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DOI：
10.1016/0092-8674(88)90221-8
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发表时间：
1988-11-18
期刊：
影响因子：
64.5
通讯作者：
BUENDIA, MA
中科院分区：
文献类型：
--
作者：
HSU, TY;MOROY, T;BUENDIA, MA
在慢性感染土拨鼠肝炎病毒的土拨鼠中诱导的两种肝细胞癌的特征在于 c-myc 附近的病毒整合和 c-myc 表达的改变。在一种肿瘤中，c-myc 外显子 3 的非翻译区域内的病毒整合导致长 c-myc 病毒共转录物的过度表达。在第二个肿瘤中，c-myc 外显子 1 上游 600 bp 处高度重排的病毒序列的单次插入与正常 c-myc mRNA 水平的增加相关。在这两种情况下，病毒增强子插入和正常 c-myc 转录或转录后控制的破坏似乎与 c-myc 激活有关。这些结果表明，如在几种逆转录病毒模型中一样，土拨鼠肝炎病毒在细胞原癌基因附近的整合可能有助于肝脏肿瘤的发生。
Two hepatocellular carcinomas, induced in wooodchucks chronically infected with woodchuck hepatitis virus, were characterized for viral integration near c-myc and alterations of c-myc expression. In one tumor, viral integration within the untranslated region of c-myc exon 3 resulted in overexpression of a long c-myc viral cotranscript. In the second tumor, a single insertion of highly rearranged viral sequences 600 bp upstream of c-myc exon 1 was associated with increased levels of normal c-myc mRNA. In both cases, viral enhancer insertion and disruption of normal c-myc transcriptional or posttranscriptional control appear to be involved in c-myc activation. These results demonstrate that integration of woodchuck hepatitis virus near a cellular proto-oncogene, as in several retroviral models, can contribute to the genesis of liver tumors.