毒理学相关资料,第八章内容参考文献5.pdfVIP

Apoptosis 2001; 6: 7–15 C 2001 Kluwer Academic Publishers The p53 tumor suppressor: Critical regulator of life death in cancer D. E. Fisher Dana-Farber Cancer Institute, Department of Pediatric Oncology Rm. D630-C, 44 Binney St., Boston, Ma 02115, USA p53 is the most commonly mutated or deleted known gene electrophoretic mobility of approximately 53kd.13 Para- in human cancer. The consequences of its disruption are doxically, initial studies suggested that p53 may func- profound, either in the germlines of patients with tion as a dominant oncogene, however careful analysis Li-Fraumeni Syndrome, or in mice with targeted gene knockouts. Abundant evidence suggests that p53 exerts revealed its role as a tumor suppressor gene together with regulation of cell cycle progression as well as apoptotic dominant activity of many mutant alleles.47 p53 mu- cell death, both in response to identical environmental tations were identified in the germ line of humans with or metabolic stressors. The specific decision of cell cy- the familial cancer predisposition condition Li-Fraumemi cle arrest vs. death may underlie p53’s differential abil- 8 Syndrome, with loss of heterozygosity at the p53 locus in ity to trigger death in cancer cells and arrest with repair in non-cancer cells, thus producing a therapeutic index tumors within these patients. In addition, mice lacking pertinent to cancer therapy. Indeed, p53 status is likely the p53 gene developed tumors at nearly 100% incidence to correlate with prognosis in many human cancers and within the first several months of age.911 Mutations in in multiple anima