Ectopic expression of KRASG12D and p53R167H in porcine mammary epithelial cells results in transformation and tumorigenesis

We describe our initial studies in the development of an orthotopic, genetically-defined, large animal model of breast cancer, using immunocompetent pigs. Primary mammary epithelial cells were isolated from the porcine gland. Primary mammary cells were immortalized with hTERT, and then transformed cell lines were generated from these immortalized cells with oncogenic KRAS and dominant negative p53. The transformed cell lines outperformed the primary cells in terms proliferation, population doubling time, soft agar growth, 2D migration, and Matrigel invasion. Three transformed cell lines were selected based on in vitro performance, and were able to grow tumors when injected subcutaneously in nude mice, with undifferentiated morphology. Tumorigenic porcine mammary cell lines were generated in this report.