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 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.
Fueyo
J
J
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Gomez-Manzano
C
C
Yung
W K
WK
Liu
T J
TJ
Alemany
R
R
McDonnell
T J
TJ
Shi
X
X
Rao
J S
JS
Levin
V A
VA
Kyritsis
A P
AP
D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression / Q000235:genetics; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D015689:Oncogene Protein p21(ras)