Tissue-specific apoptotic effects of the p53 codon 72 polymorphism in a mouse model

Currently there are several dozen human polymorphisms that have been loosely associated with cancer risk. Correlating such variants with cancer risk has been challenging, primarily due to factors such as genetic heterogeneity, contributions of diet and environmental factors, and the difficulty in ob...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2011-05, Vol.10 (9), p.1352-1355
Main Authors: Azzam, Gregory A., Frank, Amanda K., Hollstein, Monica, Murphy, Maureen E.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Codon - genetics
Cycle
Disease Models, Animal
Extra View
Gene Knock-In Techniques - methods
Genome-Wide Association Study
Humans
Landes
Mice
Mice, Mutant Strains
Neoplasms - epidemiology
Neoplasms - genetics
Neoplasms - pathology
Organogenesis
Polymorphism, Genetic - genetics
Proteins
Risk Factors
Tissue Distribution - genetics
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary:Currently there are several dozen human polymorphisms that have been loosely associated with cancer risk. Correlating such variants with cancer risk has been challenging, primarily due to factors such as genetic heterogeneity, contributions of diet and environmental factors, and the difficulty in obtaining large sample sizes for analysis. Such difficulties can be circumvented with the establishment of mouse models for human variants. Recently, several groups have modeled human cancer susceptibility polymorphisms in the mouse. Remarkably, in each case these mouse models have accurately reflected human phenotypes, and clarified the contribution of these variants to cancer risk. We recently reported on a mouse model for the codon 72 polymorphism in p53, and found that this polymorphism regulates the ability to cooperate with NF-kB and induce apoptosis. Here-in we present evidence that this polymorphism impacts the apoptotic function of p53 in a tissue-specific manner; such tissue-specific effects of polymorphic variants represent an added challenge to human cancer risk association studies. The data presented here support the premise that modeling human polymorphisms in the mouse represents a powerful tool to assess the impact of these variants on cancer risk, progression and therapy.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.10.9.15344