Beta-catenin, tcf-4, and apc interact to prevent cancer

摘要

A recombinant adenovirus (Ad-Mini-ME) which constitutively expresses the central third of APC includes all of the known beta -catenin binding repeats. When expressed in colon cancer cells, Ad-Mini-ME blocked the nuclear translocation of beta -catenin and inhibited beta -catenin/Tcf-4-mediated transactivation. Accordingly, expression of endogenous targets of the APC/ beta -catenin/Tcf-4 pathway were down-regulated. Ad-Mini-ME infection of colorectal cancer cell lines with mutant APC but wild-type beta -catenin resulted in substantial growth arrest followed by apoptosis. These findings suggest that the beta -catenin binding domain in the central third of APC is sufficient for its tumor suppresion activity.