Ianzini, F., Domann, F. E., Kosmacek, E. A., Phillips, S. L. and Mackey, M. A. Human Glioblastoma U87MG Cells Transduced with a Dominant Negative p53 (TP53) Adenovirus Construct Undergo Radiation-Induced Mitotic Catastrophe. Radiat. Res. 168, 183–192 (2007).
Human gliomas are among the most aggressive tumors, and they respond poorly to treatment. The efficacy of surgical, radiation and chemotherapy treatment of these tumors is limited by the development of resistance. Interventions aimed at altering the response of these tumors to radiation or chemotherapy treatments are needed to improve survival rate and prognosis. Glioblastomas are generally p53 (TP53) functional tumors; however, DNA repair pathways are activated in these tumors instead of the pathways to apoptosis. Thus resistance to treatment is seen in the ability of these tumors to overcome cell death. We present data that demonstrate that U87MG glioblastoma cells transduced with a dominant-negative p53 adenovirus construct become sensitized to radiation-induced mitotic catastrophe through abrogation of G2/M checkpoint control and overaccumulation of cyclin B1. These findings suggest that interventions abrogating the G2/M checkpoint sensitize these cells to radiation-induced mitotic catastrophe and may represent a novel mechanism to increase the efficacy of radiation in wild-type p53 gliomas that are resistant to apoptosis.