New APC-Like Gene Involved in Regulation of Beta-Catenin/LEF Signaling

摘要

A second adenomatous polyposis coli (APC)-like gene, APC2/APCL was recently described and localized to chromosome 19. We have fine mapped APC2 to a small region of chromosome 19p13.3 containing markers Dl 95883 and WI-19632, a region commonly lost in a variety of cancers, particularly ovarian and breast cancer. Interphase FISH analysis revealed an APC2 allelic imbalance in 19 of 20 ovarian and 4/20 breast cancers screened and indicates that APC2 could be a potential tumor suppressor gene in breast and ovarian cancer. When over- expressed in cells that express low levels of APC2, exogenous APC2 localized to the Golgi apparatus, actin-containing structures, and occasionally to microtubules. Antibodies against the N-terminus of human APC2 show that endogenous APC2 is diffusely distributed in the cytoplasm and co-localizes with both the Golgi apparatus and actin filaments. APC2 remained associated with actin filaments following treatment with the actin-disrupting agent, cytochalasin D.