Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction

Both p53 and ATM are checkpoint regulators with roles in genetic stabilizat ion and cancer susceptibility. ATM appears to function in the same DNA dama ge checkpoint pathway as p53. However, ATM's role in p53-dependent apoptosi s and tumor suppression in response to cell cycle dysregulation is unknown. In this study, we tested the role of murine ataxia telangiectasia protein (Atm) in a transgenic mouse brain tumor model in which p53-mediated apoptos is results in tumor suppression. These p53-mediated activities are induced by tissue-specific inactivation of pRb family proteins by a truncated simia n virus 40 large T antigen in brain epithelium. We show that p53-dependent apoptosis, transactivation, and tumor suppression are unaffected by Atm def iciency, suggesting that signaling in the DNA damage pathway is distinct fr om that in the oncogene induced pathway. In addition, we show that Atm defi ciency has no overall effect on tumor growth and progression in this model.