Gerard P. Zambetti (ed.)

Gebundenes Buch

The p53 Tumor Suppressor Pathway and Cancer

Beschreibung

The p53 tumor suppressor gene is mutated in approximately half of all human malignancies, including colon, lung, and breast cancers. It is well recognized that these mutations directly inactivate p53 tumor suppressor function. Furthermore, the p53 protein operates within a pathway and this pathway, including the mutations in p53, is likely inactivated by nearly every human tumor. In support of this hypothesis, 100% of mice that have been engineered such that they do not express p53 protein (knockout animals), develop highly malignant tumors by only 3-6 months of age. The importance of p53 in preventing human cancer is also evident by families in which a mutated p53 gene is inherited from a parent. Individuals who carry an inherited germline p53 mutation are associated with Li-Fraumeni syndrome. These carriers often develop cancer as children or young adults (some have multiple tumors) and remarkably, 90% of these individuals will develop cancer by 60 years of age. Lastly, cigarette smoke, sexually transmitted viruses, and other environmental hazards play a significant role in the disruption of the p53 pathway. The p53 Tumor Suppressor Pathway and Cancer provides a comprehensive review of the p53 tumor suppressor pathway, how p53 functions to prevent tumor genesis, and how this pathway is corrupted during tumor development. The latest, state-of-the-art strategies to combat cancer by targeting p53 defects in tumors is also presented.

Autor

Dr. Gerard Zambetti began working on p53 as a Damon-Runyon Postdoctoral Fellow in the laboratory of Arnie Levine at Princeton University in 1990. During his fellowship he developed the first mammalian promoter-reporter assay to monitor p53 transcriptional activity. A close colleague in the lab, Jamil Momand, identified Mdm2 as a 90 kD protein that binds wild-type p53. At the same time Donna George at Penn reported that Mdm2 promotes tumor growth. They rationalized that Mdm2 could be oncogenic by binding and inactivating p53. This hypothesis was borne out by Dr. Zambetti's demonstration that Mdm2 blocks the ability of p53 to transactivate a wild-type p53 responsive promoter-reporter. These findings established Mdm2 as a negative regulator of p53 and gave rise to the p53-Mdm2 field. Subsequent studies showed that Mdm2 inactivates p53 in human tumors. There is now a biannual international Mdm2 meeting and nearly 2000 published studies regarding Mdm2. Dr. Zambetti is presently an Associate Member at St. Jude Children's Research Hospital in Memphis, Tennessee. He has recently been involved in the identification and characterization of a novel germline p53 mutation that selectively predisposes carriers to pediatric adrenal cancer. His lab has also identified cytokine signaling pathways that repress the apoptotic function of p53. These findings could be exploited for the development of strategies to reduce the toxic side effects of radiation and chemotherapy. Dr. Zambetti also studies how p53 becomes activated during cell stress and how it kills tumor cells and his interests continue along these exciting, clinically important lines of research.

Produktdetails

• Protein Reviews 2
• Verlag: Springer, Berlin
• Artikelnr. des Verlages: 11366027
• 2005
• Seitenzahl: 260
• Erscheinungstermin: 11. Januar 2006
• Englisch
• Abmessung: 241mm x 160mm x 21mm
• Gewicht: 690g
• ISBN-13: 9780387241357
• ISBN-10: 0387241353
• Artikelnr.: 15066875