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A Genetically Defined Porcine Model of Tumorigenesis
Author(s) -
Kuzmuk Kristy,
Rund Laurie,
Adam Stacey,
Counter Christopher,
Zachary James,
Schook Lawrence
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a217-b
Subject(s) - carcinogenesis , biology , cancer research , cancer , gene , suppressor , cancer cell , genetically engineered , genetically modified organism , genetics
Our objective is to create a porcine model of cancer 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, immunocompromised 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 one of the four animals 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. This work was supported in part by USDA/NRI‐CSREES grant AG2001‐35205‐11698 and USDA‐ARS AG58‐5438‐2‐313.