The role of p53 in tumour suppression: lessons from mouse models

The use of mouse models has greatly contributed to our understanding of the role of p53 in tumour suppression. Mice homozygous for a deletion in the p 53 gene develop tumours at high frequency, providing essential evidence for the importance of p53 as a tumour suppressor. Additionally, crossing these knockout mice or transgenic expression p53 dominant negative alleles with other tumour-prone mouse strains has allowed the effect of p53 loss on tumo ur development to be examined further. In a variety of mouse models, absenc e of p53 facilitates tumorigenesis, thus providing a means to study how the lack of p53 enhances tumour development and to define genetic pathways of p53 action. Depending on the particular model system, loss of p53 either re sults in deregulated cell-cylce entry or aberrant apoptosis (programmed cel l death), confirming results found in cell culture systems and providing in sight into in vitro function of p53. Finally, as p53 null mice rapidly deve lop tumours, they are useful for evaluating agents for either chemopreventa tive or therapeutic activities.