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

J Fueyo; C Gomez-Manzano; W K Yung; T J Liu; R Alemany; T J McDonnell; X Shi; J S Rao; V A Levin; A P Kyritsis

doi:10.1038/nm0698-685

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

Nat Med. 1998 Jun;4(6):685-90. doi: 10.1038/nm0698-685.

Authors

J Fueyo¹, C Gomez-Manzano, W K Yung, T J Liu, R Alemany, T J McDonnell, X Shi, J S Rao, V A Levin, A P Kyritsis

Affiliation

¹ Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

PMID: 9623977
DOI: 10.1038/nm0698-685

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviruses, Human / genetics
Animals
Apoptosis / genetics
Apoptosis / physiology*
Carrier Proteins*
Cell Cycle Proteins / genetics
Cell Cycle Proteins / physiology
Cell Death / genetics
Cell Death / physiology
Cell Survival / genetics
Cell Survival / physiology
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology
Disease Models, Animal
E2F Transcription Factors
E2F1 Transcription Factor
Gene Expression / genetics
Genes, Tumor Suppressor
Genetic Therapy
Genetic Vectors / genetics
Glioma / genetics*
Glioma / physiopathology
Glioma / therapy
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Oncogene Protein p21(ras) / metabolism
Recombinant Fusion Proteins / genetics
Retinoblastoma Protein / metabolism
Retinoblastoma-Binding Protein 1
Transcription Factor DP1
Transcription Factors / genetics*
Transcription Factors / physiology
Transfection / genetics
Tumor Cells, Cultured

Substances

Arid4a protein, mouse
Carrier Proteins
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p16
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
E2F1 protein, human
E2f1 protein, mouse
Recombinant Fusion Proteins
Retinoblastoma Protein
Retinoblastoma-Binding Protein 1
Transcription Factor DP1
Transcription Factors
Oncogene Protein p21(ras)