Co-expression of E2F-2 enhances the p53 anti-cancer effect in human gliomacells

Gliomas are highly resistant to conventional treatment. Improved knowledge of the molecular defects of glioma cells offers new avenues for the develop ment of gene therapy strategies. Transfer of the p53 gene has proven effect ive in suppressing proliferation in human glioma cell lines. However, sever al human glioma cell lines are resistant to p53-induced cell death. The E2F family of transcription factors are pivotal for the regulation of cell-cyc le and cell-death related genes in gliomas. In the present study, we sought a more effective strategy for glioma treatment by examining the therapeuti c potential of the simultaneous transfer of p53 and E2F-2 to gliomas. Trypa n blue cell viability assays and flow,cytometric cell-cycle analysis demons trated that the transfer of both p53 and E2F-2 induced cell death in D-54 M G, a p53-resistant glioma cell line. In addition, transfer of E2F-2 did not interfere with the apoptotic properties of exogenous wild-type p53 in U-25 1 MG cells. Finally, the expression of E2F-2 in D-54 MG cells suppressed th e expression of the apoptotic: molecule mdm-2 induced by exogenous p53 in t hese cells. These results show that co-expression of E2F-2 and p53 enhances the anti-cancer effect of p53 in gliomas.