A genetic porcine model of cancer

Lawrence B. Schook, Tiago V. Collares, Wenping Hu, Ying Liang, Fernanda M. Rodrigues, Laurie A. Rund, Kyle M. Schachtschneider, Fabiana K. Seixas, Kuldeep Singh, Kevin D. Wells, Eric M. Walters, Randall S. Prather, Christopher M. Counter

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number0128864
JournalPloS one
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Schook, L. B., Collares, T. V., Hu, W., Liang, Y., Rodrigues, F. M., Rund, L. A., Schachtschneider, K. M., Seixas, F. K., Singh, K., Wells, K. D., Walters, E. M., Prather, R. S., & Counter, C. M. (2015). A genetic porcine model of cancer. PloS one, 10(7), [0128864]. https://doi.org/10.1371/journal.pone.0128864