KRAS(G12D) and TP53(R167H) Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

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  • Author: Principe, Daniel R.

    University of Illinois at Chicago, United States

  • Author: Overgaard, Nana Haahr

    T-cells & Cancer, Division of Immunology & Vaccinology, National Veterinary Institute, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Park, Alex J.

    University of Illinois at Chicago, United States

  • Author: Diaz, Andrew M.

    University of Illinois at Chicago, Denmark

  • Author: Torres, Carolina

    University of Illinois at Chicago, United States

  • Author: McKinney, Ronald

    University of Illinois at Chicago, United States

  • Author: Dorman, Matthew J.

    University of Illinois at Chicago, United States

  • Author: Castellanos, Karla

    University of Illinois at Chicago, United States

  • Author: Schwind, Regina M.

    University of Illinois at Chicago, United States

  • Author: Dawson, David W.

    California State University Los Angeles, United States

  • Author: Rana, Ajay

    Illinois State University, United States

  • Author: Maker, Ajay V.

    University of Illinois at Chicago, United States

  • Author: Munshi, Hidayatullah G.

    Northwestern University, United States

  • Author: Rund, Lauretta A.

    University of Illinois at Urbana-Champaign, United States

  • Author: J. Grippo, Paul

    University of Illinois at Chicago, United States

  • Author: Schook, Lawrence B.

    University of Illinois at Urbana-Champaign, United States

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Although survival has improved in recent years, the prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poor. Despite substantial differences in anatomy, physiology, genetics, and metabolism, the overwhelming majority of preclinical testing relies on transgenic mice. Hence, while mice have allowed for tremendous advances in cancer biology, they have been a poor predictor of drug performance/toxicity in the clinic. Given the greater similarity of sus scrofa pigs to humans, we engineered transgenic sus scrofa expressing a LSL-KRAS(G12D)-TP53(R167H) cassette. By applying Adeno-Cre to pancreatic duct cells in vitro, cells self-immortalized and established tumors in immunocompromised mice. When Adeno-Cre was administered to the main pancreatic duct in vivo, pigs developed extensive PDAC at the injection site hallmarked by excessive proliferation and desmoplastic stroma. This serves as the first large animal model of pancreatic carcinogenesis, and may allow for insight into new avenues of translational research not before possible in rodents.
Original languageEnglish
Article number12548
JournalScientific Reports
Volume8
Number of pages10
ISSN2045-2322
DOIs
Publication statusPublished - 2018

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