title: 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.
authors.affiliation: Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fueyo
authors.forename: C
authors.initials: C
authors.lastname: Gomez-Manzano
authors.forename: W K
authors.initials: WK
authors.lastname: Yung
authors.forename: T J
authors.initials: TJ
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Alemany
authors.forename: T J
authors.initials: TJ
authors.lastname: McDonnell
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: J S
authors.initials: JS
authors.lastname: Rao
authors.forename: V A
authors.initials: VA
authors.lastname: Levin
authors.forename: A P
authors.initials: AP
authors.lastname: Kyritsis
mesh_terms: 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
chemical_list: 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)