Abstract 5385: Gene expression changes downstream of APC loss predict tumor phenotype

The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated or hypermethylated in up to 70% of human breast cancer cases. Our previous studies demonstrated that Apc mutation advances the MMTV-Polyoma Middle T Antigen (PyMT) model of breast cancer, with an increase in signaling downstream of focal adhesion kinase (FAK)/Src/JNK activation in MMTV-PyMT;ApcMin/+ tumors. In addition, the majority of tumors that arose in the MMTV-PyMT;ApcMin/+ animals were classified as adenosquamous carcinoma as compared to tumors from MMTV-PyMT;Apc+/+ animals, which were solid carcinomas. Given the heterogeneous nature of these tumors, laser capture microdissection (LCM) of the adenosquamous carcinoma in MMTV-PyMT;ApcMin/+ tissues followed by quantitative real-time RT-PCR was performed to identify gene expression changes responsible for the altered tumor phenotype. In parallel studies, gene expression microarrays were performed using triplicate samples of the MMTV-PyMT;Apc+/+ and MMTV-PyMT;ApcMin/+ cell lines. RNA samples were subjected submitted to quality control via the Agilent Bioanalyzer and were hybridized to Affymetrix Mouse Genome 430 2.0 microarrays. Data analysis was performed using the Gene-Go software, and significant changes were confirmed using qRT-PCR. Multiple changes consistent with the phenotypic and proliferative changes downstream of APC loss were identified, including changes in expression of cyclooxygenase-2 (COX-2). The findings presented here indicate that APC-mediated gene expression changes can be used to predict tumor phenotype and downstream therapeutic targets. Citation Format: Andjela Pehar, Jennifer M. Cole, Jenifer R. Prosperi. Gene expression changes downstream of APC loss predict tumor phenotype. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5385. doi:10.1158/1538-7445.AM2013-5385 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.