Overexpression of E2F-1 in glioma triggers apoptosis and suppresses tumor growth in vitro and in vivo.

ABSTRACT

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