Abstract
Mdm2 and Mdm4 are critical inhibitors of the tumor suppressor p53 and keep p53 activity at bay under normal physiological conditions. Many tumors thus inactivate the p53 pathway by over producing Mdm2 and/or Mdm4. A single nucleotide polymorphism (SNP) in Mdm2 was recently identified that associates with increased levels of Mdm2 and increased risk of breast cancer in Li-Fraumeni syndrome patients. To directly test the role of SNP309 in cancer risk, we generated SNP mice and show that mice inheriting two copies of SNP309G are at increased risk of developing tumors in normal mice compared to SNP309T homozygous mice. To examine the effects of environmental factors and carcinogens, we treated these mice with a low dose of ionizing radiation or with Benzo[a]pyrene-7,8-diol-9,10-epoxide (BaP) a carcinogen found in tobacco smoke. Radiation increased the risk of cancers in SNP309G mice. However, in the skin model of BaP, the SNP309T allele conferred increased risk of papillomas. The data suggest that factors that regulate Mdm2 levels vary between different tissues and ultimately impinge on the risk of tumor development.
Citation Format: Guillermina Lozano. Factors that impinge on the p53 pathway modify cancer risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN02-01.
RSS Feeds