Identification of c- MYC as a Target of the APC Pathway

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 β-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 β-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.