Human glioblastoma U87MG cells transduced with a dominant negative p53 (TP53) adenovirus construct undergo radiation-induced mitotic catastrophe.
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 G(2)/M checkpoint control and overaccumulation of cyclin B1. These findings suggest that interventions abrogating the G(2)/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.
Ianzini
Fiorenza
F
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA. fiorenza-ianzini@uiowa.edu
Domann
Frederick E
FE
Kosmacek
Elizabeth A
EA
Phillips
Stacia L
SL
Mackey
Michael A
MA
D000256:Adenoviridae / Q000235:genetics; D016203:CDC2 Protein Kinase / Q000502:physiology; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000502:physiology; D056744:Cyclin B1; D004249:DNA Damage; D004260:DNA Repair; D016193:G1 Phase; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008938:Mitosis / Q000528:radiation effects*; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase