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The p53-Deficient Mouse as a Cancer Model

  • Chapter
Tumor Models in Cancer Research

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Among the various tumor-suppressor mouse models that have been generated since 1992 (1), the p53-knockout mouse has been the most widely used for cancer studies for a number of reasons. The p53 tumor-suppressor gene is mutated in over 50% of all human cancers, and it has been estimated that over 80% of all cancers have disruptions in p53 signaling pathways (2,3). Because loss or mutation of p53 is such a central event in the progression of human tumors, it has become perhaps the most intensively studied cancer-associated gene. Moreover, both heterozygous and nullizygous p53-deficient mice display an accelerated tumorigenesis phenotype in comparison to their wild-type p53-containing litter mates (4–7). Because of the increased sensitivity of the heterozygous p53-deficient mice to a variety of carcinogens, they are considered by the U.S. Food and Drug Administration as one of the rodent models which can be utilized in carcinogenicity assays of candidate pharmaceuticals (8). Use of the p53-deficient mice has provided important insights into p53 function in cell-cycle control, regulation of apoptosis, response to DNA damage, hypoxia, oncogenic stimuli, embryonic development, cancer biology, molecular biology, treatment, and prevention (9–13). The focus of this chapter is on the insights provided by the p53-deficient mice in cancer-related studies at the organismal level. Further discussion of the biology of p53-deficient mice is also available (9–13).

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Authors
  1. Sundaresan Venkatachalam
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  2. Stuart Tyner
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  3. Lawrence A. Donehower PhD
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  1. Lilly Research Laboratories, Indianapolis, IN, USA

    Beverly A. Teicher

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Venkatachalam, S., Tyner, S., Donehower, L.A. (2002). The p53-Deficient Mouse as a Cancer Model. In: Teicher, B.A. (eds) Tumor Models in Cancer Research. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-100-8_14

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  • DOI: https://doi.org/10.1007/978-1-59259-100-8_14

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