Abstract 1028: A mouse model of allelic loss of the core autophagy gene BECN1 in ovarian cancer

Abstract

Abstract Autophagy, a process of protein and organelle recycling, can both suppress and promote tumors. Gliomas, KRAS mutant, and BRAF driven tumor models require functional autophagy for maximal tumorigenicity and/or tumor progression. Inhibition of autophagy is able to eliminate many human cancer cell lines. However, allelic loss of the autophagy gene BECN1 is present in the majority of ovarian cancers, and BECN1 loss incurs early tumorigenesis in mouse models free of other oncogenic stimuli. Recent sequencing efforts and analyses, depending on the study, have both supported and refuted the relevance of BECN1 allelic loss in ovarian and breast cancers. To directly address the role of BECN1 allelic loss in ovarian cancer, we crossed BECN1 heterozygous knockout dams with MISIIR-TAg sires. In this model, the MISIIR promoter induces expression of large T antigen specifically in the ovarian and fallopian epithelium, inhibiting p53 activity and driving ovarian cancers in a manner befitting its human analogue. Here we present our pre-publication findings relating to the oncogenesis and progression of this murine BECN1 allelic loss model of ovarian cancer. We compare the in vivo murine results to those of in vitro human cell line models of beclin depletion, which exhibit higher basal dsDNA break repair signaling, mitochondrial stress, and reactive oxygen species generation. Citation Format: Joe R. Delaney, Chandni Patel, Dwayne G. Stupack. A mouse model of allelic loss of the core autophagy gene BECN1 in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1028.