APC2 AND BREAST CANCER

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DESCRIPTION: (Applicant's Description) A second member of the APC tumor suppressor family (APC2) was recently identified in this and other laboratories. Preliminary results show that APC2 associates with actin filaments and with the Golgi apparatus, and that like APC, APC2 is able to bind to and down-regulate beta-catenin, a member of the wnt signal transduction cascade. Although the wnt/APC/beta-catenin signaling pathway has been implicated in breast cancer no significant genetic changes in beta-catenin or APC occur in human breast cancers as they do in colon, ovarian and hepatocellular carcinomas. We have now fine mapped APC2 to a region of chromosome 19p13.3 that is subject to loss of heterozygosity (LOH) in several cancers including, most commonly, breast cancer. It is the goal of the present study to investigate the cytogenetics of this putative tumor suppressor gene. Specifically we will test the hypothesis that LOH and/or mutation of APC2 is associated with breast cancers with 19p loss. Targets of beta-catenin signaling include cyclin Dl and c-myc, both of which are commonly overexpressed in human breast cancers. We will relate the cytogenetics of APC2 to the expression of cyclin D1 and c-myc breast cancers.