Mutant p53-Driven Tumorigenesis
Most tumors inactivate the p53 tumor suppressor pathway via single nucleotide changes of the TP53 gene itself, which produces proteins with missense mutations. p53 mutant proteins clearly lose normal p53 activities. Some are partial loss of function mutations that retain some activities and probably cooperate with other changes in the p53 pathway to initiate tumor development. Many p53 mutants also exhibit gain-of-function and dominant negative properties. Several mouse models with p53 missense mutations have been generated and these now offer opportunities to study the effects of chemotherapeutic modalities.