APOPTOSIS AND APC IN COLORECTAL TUMORIGENESIS

Tumors result from disruptions in the homeostatic mechanisms that regu late cell birth and cell death. In colon cancer, one of the earliest m anifestation of this imbalance is the formation of polyps, caused by s omatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and mice. While the importance o f APC in tumorigenesis is well documented, how it functions to prevent tumors remains a mystery. Using a novel inducible expression system, we show that expression of APC in human colorectal cancer cells contai ning endogenous inactive APC alleles results in a substantial diminuti on of cell growth. Further evaluation demonstrated that this was due t o the induction of cell death through apoptosis. These results suggest that apoptosis plays a role not only in advanced tumors but also at t he very earliest stages of neoplasia.