Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

The adenomatous polyposis coli (APC) gene encodes APC tumour suppressor protein, germline mutation of which causes familial adenomatous polyposis, an autosomal intestinal cancer syndrome. We have previously demonstrated that the proto-oncogene c-Myc is essential for all the phenotypes that occur after APC loss in the murine small intestine. One caveat to this study is that it was performed in the complete absence of c-Myc. In this study, we show that heterozygosity for Myc reduces the phenotypes of APC loss and Wnt target gene expression and slows tumourigenesis. Crucially, the levels of Myc are twofold higher than wild-type levels showing that the level of Myc induced by Wnt signalling is absolutely vital for the fate of APC-deficient cells. Taken together, this suggests that c-Myc inhibition may be a viable chemoprevention strategy for colorectal cancer. Oncogene (2010) 29, 2585-2590; doi:10.1038/onc.2010.5; published online 8 February 2010