Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Genetic induction of tumorigenesis in Swine

Oncogene volume 26, pages 1038–1045 (2007)Cite this article

Abstract

The transition from basic to clinical cancer research for a number of experimental therapeutics is hampered by the lack of a genetically malleable, large animal model. To this end, we genetically engineered primary porcine cells to be tumorigenic by expression of proteins known to perturb pathways commonly corrupted in human cancer. Akin to human cells, these porcine cells were quite resistant to transformation, requiring multiple genetic changes. Moreover, the transformed porcine cells produced tumors when returned to the isogenic host animal. The ability to now rapidly and reproducibly genetically induce tumors of sizes similar to those treated clinically in a large mammal similar to humans in many respects will provide a robust cancer model for preclinical studies dependant on generating large tumors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Anderson LJ, Jarrett WF . (1968). Lymphosarcoma (leukemia) in cattle, sheep and pigs in Great Britain. Cancer 22: 398–405.

    Article  CAS  Google Scholar 

  • Armbruster BN, Banik SS, Guo C, Smith AC, Counter CM . (2001). N-terminal domains of the human telomerase catalytic subunit required for enzyme activity in vivo. Mol Cell Biol 21: 7775–7786.

    Article  CAS  Google Scholar 

  • Bos JL . (1989). Ras oncogenes in human cancer: a review. Cancer Res 49: 4682–4689.

    CAS  Google Scholar 

  • Brown DG, Johnson DF . (1970). Diseases of aged swine. J Am Vet Med Assoc 157: 1914–1918.

    CAS  PubMed  Google Scholar 

  • Chudnovsky Y, Adams AE, Robbins PB, Lin Q, Khavari PA . (2005). Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Nat Genet 37: 745–749.

    Article  CAS  Google Scholar 

  • Cifone MA, Fidler IJ . (1980). Correlation of patterns of anchorage-independent growth with in vivo behavior of cells from a murine fibrosarcoma. Proc Natl Acad Sci USA 77: 1039–1043.

    Article  CAS  Google Scholar 

  • Dewhirst MD, Thrall D, Macewen E . (2000). Spontaneous Pet Animal Cancers. In: Teicher BA (ed). Tumor Models in Cancer Research. Humana Press: Totowa, NJ pp 565–589.

    Google Scholar 

  • Fiebig H-H, Burger AM . (2000). Tumor Xenografts and Explants. In: Teicher BA (ed). Tumor Models in Cancer Research. Humana Press: Totowa, NJ, pp 113–141.

    Google Scholar 

  • Goessel G, Quante M, Hahn WC, Harada H, Heeg S, Suliman Y et al. (2005). Creating oral squamous cancer cells: a cellular model of oral-esophageal carcinogenesis. Proc Natl Acad Sci USA 102: 15599–15604.

    Article  CAS  Google Scholar 

  • Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA . (1999). Creation of human tumour cells with defined genetic elements. Nature 400: 464–468.

    Article  CAS  Google Scholar 

  • Hahn WC, Dessain SK, Brooks MW, King JE, Elenbaas B, Sabatini DM et al. (2002). Enumeration of the simian virus 40 early region elements necessary for human cell transformation. Mol Cell Biol 22: 2111–2123.

    Article  CAS  Google Scholar 

  • Hamad NM, Elconin JH, Karnoub AE, Bai W, Rich JN, Abraham RT et al. (2002). Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev 16: 2045–2057.

    Article  CAS  Google Scholar 

  • Kendall SD, Adam SJ, Counter CM . (2006). Genetically engineered human cancer models utilizing mammalian transgene expression. Cell Cycle 5: 1074–1079.

    Article  CAS  Google Scholar 

  • Kendall SD, Linardic CM, Adam SJ, Counter CM . (2005). A network of genetic events sufficient to convert normal human cells to a tumorigenic state. Cancer Res 65: 9824–9828.

    Article  CAS  Google Scholar 

  • Levine AJ . (1997). p53, the cellular gatekeeper for growth and division. Cell 88: 323–331.

    Article  CAS  Google Scholar 

  • Lim KH, Counter CM . (2004). Leveling the playing field. Mol Cell 15: 491–492.

    Article  CAS  Google Scholar 

  • Nesbit CE, Tersak JM, Prochownik EV . (1999). MYC oncogenes and human neoplastic disease. Oncogene 18: 3004–3016.

    Article  CAS  Google Scholar 

  • O'Hayer KM, Counter CM . (2006). A genetically defined normal somatic human cell system to study ras oncogenesis in vitro and in vivo. In: Abelson JN, Simon MI (eds). Methods in Enzymology. In: Balch WE, Der CJ, Hall A (eds). Regulators and effectors of small GTPases: Ras family, vol. 407. Academic Press: San Diego. pp 637–647.

    Google Scholar 

  • Oxenhandler RW, Berkelhammer J, Smith GD, Hook Jr RR . (1982). Growth and regression of cutaneous melanomas in Sinclair miniature swine. Am J Pathol 109: 259–269.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pathak S, Multani AS, McConkey DJ, Imam AS, Amoss Jr MS . (2000). Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion. Int J Oncol 17: 1219–1224.

    CAS  PubMed  Google Scholar 

  • Perez J, Garcia PM, Bautista MJ, Millan Y, Ordas J, Martin de las Mulas J . (2002). Immunohistochemical characterization of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic tumors of Duroc and Iberian swine. Vet Pathol 39: 445–451.

    Article  CAS  Google Scholar 

  • Rangarajan A, Hong SJ, Gifford A, Weinberg RA . (2004). Species- and cell type-specific requirements for cellular transformation. Cancer Cell 6: 171–183.

    Article  CAS  Google Scholar 

  • Shay JW, Wright WE . (2002). Telomerase: a target for cancer therapeutics. Cancer Cell 2: 257–265.

    Article  CAS  Google Scholar 

  • Stewart SA, Weinberg RA . (2000). Telomerase and human tumorigenesis. Semin Cancer Biol 10: 399–406.

    Article  CAS  Google Scholar 

  • Swanson KS, Mazur MJ, Vashisht K, Rund LA, Beever JE, Counter CM et al. (2004). Genomics and clinical medicine: rationale for creating and effectively evaluating animal models. Exp Biol Med (Maywood) 229: 866–875.

    Article  CAS  Google Scholar 

  • Van Dyke T, Jacks T . (2002). Cancer modeling in the modern era: progress and challenges. Cell 108: 135–144.

    Article  CAS  Google Scholar 

  • Vincent-Naulleau S, Le Chalony C, Leplat J-J, Bouet S, Bailly C, Spatz A et al. (2004). Clinical and histopathological characterization of cutaneous melanomas in the melanoblastoma-bearing libechov minipig model. Pigment Cell Res 17: 24–35.

    Article  Google Scholar 

  • Wargovich MJ, Satterfield W, Price RE, Stephens LC, Coghlan L . (1991). Hepatic pathology of the colon carcinogen, azoxymethane, in Hanford-Moore miniature pigs. J Comp Pathol 105: 271–278.

    Article  CAS  Google Scholar 

  • Weinberg RA . (1991). Tumor suppressor genes. Science 254: 1138–1146.

    Article  CAS  Google Scholar 

  • Xie W, Evans RM . (2002). Pharmaceutical use of mouse models humanized for the xenobiotic receptor. Drug Discov Today 7: 509–515.

    Article  CAS  Google Scholar 

  • Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, Ivaldi G et al. (2004). A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol 6: 308–318.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank C Linardic, D Kendall, G Ivaldi, J Beever, N Hamad, I York, J Sedivy and M Dewhirst for advice or assistance and AR Means for support. We also thank the Histopathology Laboratory, College of Veterinary Medicine, University of Illinois. This work was supported by grants from the Elsa U Pardee Foundation, Duke Comprehensive Cancer Center, NIH (CA94184) and USDA (2002-35205-12712). CMC is Leukemia and Lymphoma Scholar, LAR is supported by a Cargill Research Fellowship. SJA is supported by a DoD Predoctoral Training Fellowship (BC050468).

Author information

Author notes

  1. S J Adam and L A Rund: These two authors contributed equally this work.

Authors and Affiliations

  1. Department of Pharmacology and Cancer Biology, Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

    S J Adam & C M Counter

  2. Department of Animal Sciences and Institute for Genomic Biology, University of Illinois, Urbana, IL, USA

    L A Rund, K N Kuzmuk & L B Schook

  3. Department of Pathobiology, University of Illinois, Urbana, IL, USA

    J F Zachary

Authors
  1. S J Adam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L A Rund
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K N Kuzmuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J F Zachary
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L B Schook
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C M Counter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to L B Schook or C M Counter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adam, S., Rund, L., Kuzmuk, K. et al. Genetic induction of tumorigenesis in Swine. Oncogene 26, 1038–1045 (2007). https://doi.org/10.1038/sj.onc.1209892

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209892

Keywords

This article is cited by

Search

Advanced search

Quick links