Identification of c- <i>MYC</i> as a Target of the APC Pathway
Tong‐Chuan He(Johns Hopkins University), Andrew B. Sparks(Johns Hopkins University), Carlo Rago(Johns Hopkins University), Heiko Hermeking(Johns Hopkins University), Leigh Zawel(Johns Hopkins University), Luís Teixeira da Costa(Johns Hopkins University), Patrice J. Morin(Johns Hopkins University), Bert Vogelstein(Johns Hopkins University), Kenneth W. Kinzler(Johns Hopkins University)
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Abstract
The adenomatous polyposis coli 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.
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