Polyamines pp 129-141 | Cite as

Carcinogenesis Studies in Mice with Genetically Engineered Alterations in Polyamine Metabolism

  • David J. FeithEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 720)


Polyamines are intimately linked to essential cellular processes that are required for cell growth and ­proliferation, and abundant evidence links polyamine metabolism to tumor susceptibility and progression. Intensive efforts over the past 2 decades have yielded numerous mouse models of cancer that utilize genetic manipulations to recapitulate the molecular alterations and cellular interactions that characterize human cancers. These models provide the ideal genetic context to examine the impact of altered polyamine content on tumor biology, with the goal of applying the knowledge acquired in mice to the prevention and treatment of human cancer. Transgenic and knockout mouse technologies allow the investigator to enhance or delete, respectively, the expression of a given polyamine metabolic enzyme or regulatory protein, and advanced models facilitate both temporal and spatial control of gene expression in the mouse. These methods can be utilized to modulate total polyamine content or relative polyamine ratios in specific cell populations in vivo and evaluate the impact of this manipulation on tumor appearance and progression. This chapter provides resources to identify existing mouse strains that exhibit increased susceptibility to tumor development as well as strains that were engineered for increased or decreased expression of polyamine regulatory proteins. A conceptual framework is then presented to combine these resources in order to successfully complete a carcinogenesis study in mice with altered polyamine metabolism.

Key words

Polyamine Transgenic mice Knockout mice Conditional transgene Conditional knockout Carcinogenesis Mouse models of cancer 



The author thanks Patricia Welsh for her outstanding technical expertise in the maintenance of mouse strains and utilization of mouse models of cancer in his laboratory.


  1. 1.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedCrossRefGoogle Scholar
  2. 2.
    Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458:719–724PubMedCrossRefGoogle Scholar
  3. 3.
    Van Dyke T, Jacks T (2002) Cancer modeling in the modern era: progress and challenges. Cell 108:135–144PubMedCrossRefGoogle Scholar
  4. 4.
    Nagy A, Gertesenstein M, Vintersten K, Behringer R (2003) Manipulating the mouse embryo: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  5. 5.
    Lewandoski M (2001) Conditional control of gene expression in the mouse. Nat Rev Genet 2:743–755PubMedCrossRefGoogle Scholar
  6. 6.
    Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26:99–109PubMedCrossRefGoogle Scholar
  7. 7.
    Tuveson DA, Jacks T (2002) Technologically advanced cancer modeling in mice. Curr Opin Genet Dev 12:105–110PubMedCrossRefGoogle Scholar
  8. 8.
    Rangarajan A, Weinberg RA (2003) Opinion: comparative biology of mouse versus human cells: modelling human cancer in mice. Nat Rev Cancer 3:952–959PubMedCrossRefGoogle Scholar
  9. 9.
    Casero RA Jr, Marton LJ (2007) Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov 6:373–390PubMedCrossRefGoogle Scholar
  10. 10.
    Gerner EW, Meyskens FL Jr (2004) Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 4:781–792PubMedCrossRefGoogle Scholar
  11. 11.
    Gilmour SK (2007) Polyamines and nonmelanoma skin cancer. Toxicol Appl Pharmacol 224:249–256PubMedCrossRefGoogle Scholar
  12. 12.
    Janne J, Alhonen L, Pietila M, Keinanen TA, Uimari A, Hyvonen MT, Pirinen E, Jarvinen A (2006) Genetic manipulation of polyamine catabolism in rodents. J Biochem 139:155–160PubMedCrossRefGoogle Scholar
  13. 13.
    Pegg AE, Feith DJ (2007) Polyamines and neoplastic growth. Biochem Soc Trans 35:295–299PubMedCrossRefGoogle Scholar
  14. 14.
    Abel EL, Angel JM, Kiguchi K, DiGiovanni J (2009) Multi-stage chemical carcinogenesis in mouse skin: fundamentals and applications. Nat Protoc 4:1350–1362PubMedCrossRefGoogle Scholar
  15. 15.
    Shoemaker AR, Gould KA, Luongo C, Moser AR, Dove WF (1997) Studies of neoplasia in the Min mouse. Biochim Biophys Acta 1332:F25–F48PubMedGoogle Scholar
  16. 16.
    Janne J, Alhonen L, Pietila M, Keinanen TA (2004) Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem 271:877–894PubMedCrossRefGoogle Scholar
  17. 17.
    Lyons SK (2005) Advances in imaging mouse tumour models in vivo. J Pathol 205:194–205PubMedCrossRefGoogle Scholar
  18. 18.
    Zinn KR, Chaudhuri TR, Szafran AA, O’Quinn D, Weaver C, Dugger K, Lamar D, Kesterson RA, Wang X, Frank SJ (2008) Noninvasive bioluminescence imaging in small animals. ILAR J 49:103–115PubMedGoogle Scholar
  19. 19.
    Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5:796–806PubMedCrossRefGoogle Scholar
  20. 20.
    Morgan DML (ed) (1998) Polyamine protocols. In: Methods in molecular biology, vol 79. Humana Press, TotowaGoogle Scholar
  21. 21.
    Balmain A (2002) Cancer as a complex genetic trait: tumor susceptibility in humans and mouse models. Cell 108:145–152PubMedCrossRefGoogle Scholar
  22. 22.
    George K, Iacobucci A, Uitto J, O’Brien TG (2005) Identification of an X-linked locus modifying mouse skin tumor susceptibility. Mol Carcinog 44:212–218PubMedCrossRefGoogle Scholar
  23. 23.
    Wallace J (2000) Humane endpoints and cancer research. ILAR J 41:87–93PubMedGoogle Scholar
  24. 24.
    Matsufuji S, Matsufuji T, Miyazaki Y, Murakami Y, Atkins JF, Gesteland RF, Hayashi S (1995) Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme. Cell 80:51–60PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Cellular and Molecular PhysiologyPennsylvania State University College of MedicineHersheyUSA

Personalised recommendations