Role of c-Myc in Apc Mutant Intestinal Phenotype: Case Closed or Time for a New Beginning?

Inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene occurs in most colorectal cancers. The proto-oncogene c-MYC was one of the first genes linked to APC inactivation, but the in vivo significance of c-MYC's enhanced expression in intestinal cells with APC defects has been uncertain. Sansom et al. recently reported that targeted inactivation of c-Myc in murine intestinal epithelium potently inhibited phenotypical and transcriptional changes seen in Apc-deficient intestinal epithelium. While these findings are very interesting, some questions remain about the assignment of c-Myc as the pre-eminent β-catenin-regulated gene in intestinal epithelium.