Abstract:
Our objective is to create a porcine model representative of human cancers. Genetically engineered tumors in pigs may prove to be invaluable in the future for determining the efficacy of anti-cancer drugs and to study the process of tumorigenesis and cancer in a genetically compliant animal model that is physiologically more similar to humans than rodents. Genetic engineering of the porcine cancer cells was based on how human cells are driven to a tumorigenic state via the enforced expression of proteins that disrupt the p53 tumor suppressor pathway and activate the c-Myc and Ras pathways, all of which are commonly corrupted in human cancers. Four genes (cyclin D1, CDK 4, c-Myc, and H-Ras) were introduced into cultured porcine fibroblasts using retroviral vectors. Tumorigenic porcine cells were injected into isogenic, immune-compromised pigs to test for tumor growth. Tumors formed but quickly regressed when immune suppression was removed. In an attempt to induce a less immunogenic tumor, pigs were infected directly with two retroviruses carrying these four genes. This method induced lymphosarcoma in all of the animals (n = 6) in the absence of immunosuppression. Future studies will attempt to induce tumors in cloned animals, thus producing tumors that can be transferred to any number of identical animals to study the process of tumorigenesis and cancer phenotypes.