Tissue-specific tumour suppression by APC.

One question that has been central to the study of the Apc gene is why the Apc gene is mutated so frequently in colorectal cancer but relatively infrequently in other tumour types. This chapter reviews recent data obtained in mice after conditional deletion of both copies of the Apc gene from adult epithelial tissues with particular focus on the intestinal epithelium. These data suggest that a major reason for the frequent mutation of Apc in colorectal cancer lies in the distinct character of the intestinal epithelium where Apc loss leads to a progenitor-like phenotype. Thus intestinal enterocytes lacking Apc escape the two major selective constraints that usually prevent cells from becoming cancerous in the intestine: they fail to differentiate and fail to migrate so are not sloughed off into the intestinal lumen.