Fueyo J, Gomez-Manzano C, Yung W K, Liu T J, Alemany R, McDonnell T J, Shi X, Rao J S, Levin V A, Kyritsis A P
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Nat Med. 1998 Jun;4(6):685-90. doi: 10.1038/nm0698-685.
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.