Abstract 78: A novel orthotopic mammary epithelial cell (MEC) transplantation model of breast cancer formation

Abstract

Abstract The pathogenesis of breast cancer is polygenic. Exploring the involvement of different onco- and tumor suppressor genes, and combinations of these genes, in early breast cancer formation is important for understanding the natural history of the disease. Preclinical studies of the fundamental biological and metabolic changes that occur during breast oncogenesis in currently available transgenic mouse models are limited by the requirement for tissue-specific promoters and the random nature of tumor formation. The mouse mammary gland is a unique organ in that most of its development occurs after birth. Moreover, isolated mammary epithelial cells (MECs) have the capacity to regenerate a functional gland upon orthotopic transplantation into the cleared fat pad of a syngeneic recipient. We describe here a new transplantation system using pure MECs derived from genetically engineered mice harboring floxed oncogenes. First we selected in vitro for a stromal and hematopoietic cell-free MEC preparation. In the MEC donor transgenic strains the activation of oncogenes (K-Ras, c-Myc) or the deletion of tumor suppressors (p53) is dependent on Cre recombinase expression (Cre-lox system). Using an adenoviral Cre-recombinase vector we activated these oncogenic changes in isolated MECs. Colony formation assays demonstrated the viability of these mixed transduced/non-transduced MEC populations. Following transplantation into the cleared fat pad of syngeneic mice the transduced MECs preserved their fat pad repopulating and duct forming potential and the induced oncogenic changes resulted in mammary tumor formation. This proposed system offers tissue specific promoter-free and lactation independent spatial control of oncogenic events in the epithelial cell compartment of breast ducts. Citation Format: Zoltan Szucs, Michael D. Prater, John Stingl, Kevin M. Brindle. A novel orthotopic mammary epithelial cell (MEC) transplantation model of breast cancer formation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 78. doi:10.1158/1538-7445.AM2014-78