RECENT PROGRESS ON THE ROLE OF APC PROTEI N IN THE ORIGIN OF COLORECTAL-CANCER

The adenomatous polyposis coli (APC) gene has been found to be mutated during the development of sporadic colorectal cancers as well as in f amilial adenomatous polyposis (FAP). These conditions result from init ially somatic and germ line mutations respectively. In both cases, the expressed protein in truncated at its carboxyterminal region. Investi gations into the role of wild-type APC have led to a better understand ing of the importance of mutations in the genesis and progression of a denomas. APC was shown to regulate cell growth and cell death, to bind beta-catenin, and to colocalize with microtubules. APC truncation was therefore hypothesized to alter cell multiplication and cells are no longer able to undergo apoptosis. Owing to its beta-catenin binding, A PC can modify the pool of beta-catenin which is in part utilized in th e assembly of adherens junctions and in nuclear signalling. Finally, A PC involvement in microtubule-dependent locomotion may explain some ch anges in cell movement which are observed in adenomas. The establishem ent of murine mutants and of normal and malignant intestinal cell cult ures have allowed to assess biochemical and physiological properties o f APC and its putative role in the genesis of colorectal carcinogenesi s. Moreover, these experimental models have suggested a variety of pos sible therapeutic approaches.