Identification of c-MYC as a target of the APC pathway
Identification of c-MYC as a target of the APC pathway
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DOI：
10.1126/science.281.5382.1509
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发表时间：
1998-09-04
期刊：
影响因子：
56.9
通讯作者：
Kinzler, KW
中科院分区：
文献类型：
--
作者：
He, TC;Sparks, AB;Kinzler, KW
腺瘤性息肉病螺旋基因（APC）是一种在大多数结直肠癌中失活的肿瘤抑制基因。APC的突变导致β-连环蛋白的异常积累，然后结合T细胞因子-4（Tcf-4），导致未知基因的转录激活增加。在此，c-MYC癌基因被鉴定为该信号通路中的靶基因。c-MYC的表达被野生型APC抑制并被β-连环蛋白激活，这些作用通过c-MYC启动子中的Tcf-4结合位点介导。这些结果为理解先前在结直肠癌中c-MYC的神秘过度表达提供了分子框架。
The adenomatous polyposis coil gene (APC) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of APC cause aberrant accumulation of beta-catenin, which then binds T cell factor-4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated by beta-catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.