Effect of Anti-Apoptotic Pathway Inhibition on Cancer Development in Non-Homologous End Joining DNA Repair Deficient Mouse Models
Our genomic stability is constantly threaten by internal and external agents. Among DNA damages, double strand breaks (DSBs) are the most detrimental but also beneficial, as they are required to generate the antibody variety in pro-B and T lymphocytes. These damages are mainly solved by non-homologous end join DNA repair (NHEJ). Failures in NHEJ repair leads to genomic rearrangements and cancer. To avoid this undesired fate, DNA damaged cells undergo p53-dependent apoptosis. In fact, p53-deficient mice display accelerated ratios of tumorigenesis early in life. In this context, the combined deficiency of NHEJ factors and p53 has been strongly related with cancer, pointedly medulloblastoma. Contrary p53, Bcl-2 proteins lead to a blockage in apoptosis. Actually, the inhibition of Bcl-2 proteins may prevent cancer development.
Here, we propose to determine to what extent NHEJ factors are involved in cancer development as well as the efficiency of Bcl-2 inhibitor for cancer prevention. To achieve our goals we have design an in vivo study on different NHEJ-deficient mouse models, being p53-deficient and wild type mice as controls. Each mouse genotype will be comprised by two subgroups: treated and untreated, with Bcl-2 inhibitor.
Here, we propose to determine to what extent NHEJ factors are involved in cancer development as well as the efficiency of Bcl-2 inhibitor for cancer prevention. To achieve our goals we have design an in vivo study on different NHEJ-deficient mouse models, being p53-deficient and wild type mice as controls. Each mouse genotype will be comprised by two subgroups: treated and untreated, with Bcl-2 inhibitor.