Antisense ATM gene therapy: a strategy to increase the radiosensitivity ofhuman tumors

Atm, the gene mutated in ataxia-telangiectasia (AT)patients, is an essentia l component of the signal transduction pathway that responds to DNA damage due to ionizing radiation (IR). We attenuated ATM protein expression in hum an glioblastoma cells by expressing antisense RNA to a functional domain of the atm gene. While ATM expression decreased, constitutive expression of p 53 and p21 increased. Irradiated ATM-attenuated cells failed to induce p53, demonstrated radioresistant DNA synthesis, and increased radiosensitivity. Antisense-ATM gene therapy in conjunction with radiation therapy may provi de a novel strategy for the treatment of cancer.