Identification of c-MYC as a target of the APC pathway

Tong Chuan He, Andrew B. Sparks, Carlo Rago, Heiko Hermeking, Leigh Zawel, Luis T. Da Costa, Patrice J. Morin, Bert Vogelstein, Kenneth W. Kinzler

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1509-1512
Number of pages4
JournalScience
Volume281
Issue number5382
DOIs
StatePublished - Sep 4 1998
Externally publishedYes

ASJC Scopus subject areas

  • General

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