1. Academic Validation
  2. Identification of c-MYC as a target of the APC pathway

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

  • Science. 1998 Sep 4;281(5382):1509-12. doi: 10.1126/science.281.5382.1509.
T C He 1 A B Sparks C Rago H Hermeking L Zawel L T da Costa P J Morin B Vogelstein K W Kinzler
Affiliations

Affiliation

  • 1 Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
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.

Figures