p53 and human cancers.

Mutations in the p53 gene are one of the commonest specific genetic changes found in human cancer. The p53 gene is not required for normal development but lack of p53 function confers an enormously elevated risk of developing cancer, thus it seems truly to act as a tumour suppressor gene. The p53 protein is normally present in minute amounts in cells but when cells are exposed to genotoxic stimuli p53 levels rise rapidly and initiate a programme of cell death, probably by means of transcriptional regulation. This response is lost in many tumour cells as they have either inactivated their p53 genes by mutation or blocked the activity of p53 through the production of proteins that bind to it and neutralise it. Mutant p53 proteins accumulate to high levels in many cancer cells and the p53 protein and the p53 response to DNA damage represent key points for therapeutic intervention.