OVEREXPRESSION OF E2F-1 IN GLIOMA TRIGGERS APOPTOSIS AND SUPPRESSES TUMOR-GROWTH IN-VITRO AND IN-VIVO

The transfer of apoptosis genes to tumors is one of the most promising strategies for cancer gene therapy. We have shown that massive apopto sis occurs when wild-type p53 expression is induced in glioma cells ca rrying a p53 gene mutation. However, adenovirus-mediated p53 gene tran sfer is ineffective in causing apoptosis in glioma cells that retain a wild-type p53 genotype. We evaluated the effect of E2F-1 overexpressi on on the growth of gliomas in vitro and in vivo. In the in vitro stud y, the adenovirus-mediated transfer of exogenous E2F-1 protein precipi tated generalized apoptosis in gliomas. The treatment with Ad5CMV-E2F- 1 of nude mice carrying subcutaneous gliomas arrested tumor growth. Ou r results indicate that E2F-1 has anti-glioma activity in vitro and in vivo.