Human APC2 localization and allelic imbalance

A second adenomatous polyposis coli (APC)-like gene, APC2/APCL, was recentl y described and localized to chromosome 19. We have fine mapped APC2 to a s mall region of chromosome 19p13.3 containing markers D19S883 and WI-19632, a region commonly lost in a variety of cancers, particularly ovarian cancer . Interphase fluorescence in situ hybridization analysis revealed an APC2 a llelic imbalance in 19 of 20 ovarian cancers screened and indicates that AP C2 could be a potential tumor suppressor gene in ovarian cancer. When overe xpressed in SKOV3 ovarian cancer cells, which express low levels of APC2, e xogenous APC2 localized to the Golgi apparatus, actin-containing structures , and occasionally to microtubules. Antibodies against the NH2 terminus of human APC2 show that endogenous APC2 is diffusely distributed in the cytopl asm and colocalizes with both the Golgi apparatus and actin filaments. APC2 remained associated with actin filaments after treatment with the actin-di srupting agent, cytochalasin D. These results suggest that APC2 is involved in actin-associated events and could influence cell motility or adhesion t hrough interaction with actin filaments, as well as functioning independent ly or in cooperation with APC to down-regulate beta -catenin signaling.