title: Enhanced cancer cell killing by truncated E2F-1 used in combination with oncolytic adenovirus.
abstract: Adenovirus-mediated gene transfer into a tumor mass can be improved by combining it with conditionally-replicating adenovirus (CRAd) when both vectors co-infect the same cancer cell. We investigated the efficiency of enhancing transgene expression and effectiveness of cancer killing of two advenoviruses (Ads), one expressing E2F-1 (AdE2F-1) and another expressing a truncated form of E2F-1 that lacks the transactivation domain (AdE2Ftr), when combined with oncolytic Adhz60. We found that AdE2F-1 with Adhz60 actually decreased E2F-1 expression and viral replication through a mechanism apparently involving repression of the cyclin-E promoter and decreased expression of early and late structural proteins necessary for viral replication. In contrast, AdE2Ftr with Adhz60 resulted in increased E2Ftr expression, AdE2Ftr replication, and cancer cell death both in vitro and in vivo. These results indicate that AdE2Ftr coupled with a CRAd enhances AdE2Ftr-mediated cancer cell death.
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Gomez-Gutierrez
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Rao
authors.forename: Heshan Sam
authors.initials: HS
authors.lastname: Zhou
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic; D014161:Transduction, Genetic; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D017500:Adenovirus E1A Proteins; D019927:Cyclin E; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human