title: A Genetic Porcine Model of Cancer.
abstract: The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic "oncopig" line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into immunocompromised mice. Finally, injection of AdCre directly into these oncopigs led to the rapid and reproducible tumor development of mesenchymal origin. Transgenic animals receiving AdGFP (green fluorescent protein) did not have any tumor mass formation or altered histopathology. This oncopig line could thus serve as a genetically malleable model for potentially a wide spectrum of cancers, while controlling for temporal or spatial genesis, which should prove invaluable to studies previously hampered by the lack of a large animal model of cancer.
authors.affiliation: Department of Animal Sciences, University of Illinois, Champaign-Urbana, Illinois, United States of America; Department of Bioengineering, University of Illinois, Champaign-Urbana, Illinois, United States of America; Department of Surgery, University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schook
authors.affiliation: Technology Development Center, Postgraduate Program in Biotechnology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Tiago V
authors.initials: TV
authors.lastname: Collares
authors.affiliation: State Key Laboratory of AgroBiotechnology, China Agricultural University, Beijing, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Animal Sciences, University of Illinois, Champaign-Urbana, Illinois, United States of America.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Rodrigues
authors.affiliation: Department of Animal Sciences, University of Illinois, Champaign-Urbana, Illinois, United States of America.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Rund
authors.affiliation: Department of Animal Sciences, University of Illinois, Champaign-Urbana, Illinois, United States of America.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Schachtschneider
authors.affiliation: Technology Development Center, Postgraduate Program in Biotechnology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Fabiana K
authors.initials: FK
authors.lastname: Seixas
authors.affiliation: Veterinary Diagnostic Laboratory, University of Illinois, Champaign-Urbana, Illinois, United States of America.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Singh
authors.affiliation: Division of Animal Science, National Swine Research and Resource Center, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Wells
authors.affiliation: Division of Animal Science, National Swine Research and Resource Center, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Walters
authors.affiliation: Division of Animal Science, National Swine Research and Resource Center, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Prather
authors.affiliation: Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Counter
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D017930:Genes, Reporter; D016158:Genes, p53; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D064593:Heterografts; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D013552:Swine; D015533:Transcriptional Activation; D019076:Transgenes