Imprinted M6p/Igf2 receptor is mutated in rat liver tumors
Imprinted M6p/Igf2 receptor is mutated in rat liver tumors
复制标题
DOI：
10.1038/sj.onc.1201801
复制
发表时间：
1998-05-28
期刊：
影响因子：
8
通讯作者：
Jirtle, RL
中科院分区：
文献类型：
--
作者：
Mills, JJ;Falls, JG;Jirtle, RL
我们之前已经证明，甘露糖6-磷酸/胰岛素样生长因子2受体(M6P/IGF2R)失活是人类肝癌和乳腺癌发生的常见早期事件。M6P/Igf2r在小鼠中是印记的，而在大多数人类中表达是双等位基因。在这项研究中，M6P/Igf2r基因也被印记在Fischer 344、Lewis和Brown挪威大鼠的肝脏中。此外，我们还在40%的二乙基亚硝胺引发的大鼠肝肿瘤中发现了M6P/Igf2r等位基因的突变。这些结果为M6P/IGF2R作为肝癌抑制基因提供了进一步的证据。他们还表明，小鼠和大鼠对那些M6P/Igf2r机械参与转化的肝癌致癌物比人类更敏感，因为需要灭活一个而不是两个等位基因。
We have previously shown that inactivation of mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/ IGF2R) is a common early event in both human liver and breast carcinogenesis. The M6p/Igf2r is imprinted in mice while expression is biallelic in most humans. In this investigation the M6p/Igf2r gene is shown to also be imprinted in the liver of Fischer 344, Lewis and Brown Norway rats. In addition, we have identified mutations in the expressed allele of the M6p/Igf2r in 40% of diethylnitrosamine-initiated rat liver tumors. These results provide further evidence that the M6P/IGF2R functions as a liver tumor suppressor gene. They also suggest that mice and rats would be more sensitive than humans to those hepatocarcinogens in which the M6p/ Igf2r is mechanistically involved in transformation since one rather than two alleles would need to be inactivated.