The p53 tumor suppressor: critical regulator of life & death in cancer.
p53 is the most commonly mutated or deleted known gene in human cancer. The consequences of its disruption are profound, either in the germlines of patients with Li-Fraumeni Syndrome, or in mice with targeted gene knockouts. Abundant evidence suggests that p53 exerts regulation of cell cycle progression as well as apoptotic cell death, both in response to identical environmental or metabolic stressors. The specific decision of cell cycle arrest vs. death may underlie p53's differential ability to trigger death in cancer cells and arrest with repair in non-cancer cells, thus producing a therapeutic index pertinent to cancer therapy. Indeed, p53 status is likely to correlate with prognosis in many human cancers and in multiple animal tumor models. The mechanistic basis for p53's functions are still emerging, and will hopefully yield new therapeutic strategies applicable to treatment of the many poor-prognosis, p53-deficient human malignancies.
Fisher
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Dana-Farber Cancer Institute, Department of Pediatric Oncology, Boston, MA 02115, USA.
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*