Model of ATM-MPG–mediated therapeutic resistance in pGBM.

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Model of ATM-MPG–mediated therapeutic resistance in pGBM. Model of ATM-MPG–mediated therapeutic resistance in pGBM. A, Western blot analysis demonstrating MPG knockdown by retroviral shRNA transduction and ATM knockdown by siRNA at 72 hours. Control cells were transduced with shRNA control retrovirus and treated with siRNA scramble controls. B, control or double MPG and ATM knockdown astrocytes were treated with 100 μmol/L temozolomide (TMZ) and assessed for viability at 72 hours. ns, nonsignificance. C, control or double MPG and ATM knockdown astrocytes were targeted by siRNA for DNA damage response genes redundant to either ATM or MPG and treated with 100 μmol/L temozolomide and assessed for viability at 72 hours. All experiments were performed in triplicate with the SEM reported. D, summary model of targeting the BER and ATM pathways for sensitization to alkylating agents. MA, methoxyamine. Sameer Agnihotri et al. Cancer Discovery 2014;4:1198-1213 ©2014 by American Association for Cancer Research