Carcinogenesis Studies in Mice with Genetically Engineered Alterations in Polyamine Metabolism

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.