Insertion of an exogenous promoter in the E1A regulatory region of adenovirus does not disturb viral replication despite reduced E1A transcription

Insertion of an exogenous promoter into adenoviral regulatory regions may result in altered specificity and activity of the integrated promoter-mediated transcription in the context of recombinant adenoviruses (Ad). The alteration is due to the influence of the viral regulatory elements. Specificity...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2004-01, Vol.203 (1), p.51-57
Main Authors: Yu, Ling, Hamada, Katsuyuki, Namba, Masayoshi, Kadomatsu, Kenji, Muramatsu, Takashi, Matsubara, Shuichiro, Tagawa, Masatoshi
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenovirus
Adenovirus E1A Proteins - genetics
Adenoviruses
Cell growth
Cells, Cultured
Cloning
Cytotoxicity
Deoxyribonucleic acid
DNA
E1A
Gene expression
Gene Expression Regulation, Viral
Genes, Viral
Genomes
Humans
Luciferase assay
Promoter
Promoter Regions, Genetic
Regulatory Sequences, Nucleic Acid
Studies
Transcription, Genetic
Transfection
Tumors
Variance analysis
Viral replication
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Insertion of an exogenous promoter into adenoviral regulatory regions may result in altered specificity and activity of the integrated promoter-mediated transcription in the context of recombinant adenoviruses (Ad). The alteration is due to the influence of the viral regulatory elements. Specificity of oncolytic Ad, in which the E1A expression is designed to be controlled by a tumor-specific promoter, could thus be modulated by the Ad E1A enhancer/promoters. We prepared recombinant Ad bearing a midkine (MK) promoter region in the 3′-side of the E1A promoter and investigated the relationship between transcriptional activity by the E1A promoter-fused MK fragment and the viral replication. Reporter assays revealed that the transcriptional activity of the fused E1A-MK fragment was significantly lower than that of respective E1A and the MK promoters. However, the replication of the Ad bearing the MK promoter was greater than or comparable to that of wild-type Ad. The present study suggests that the replication of oncolytic Ad in tumors is not directly correlated with the promoter activity to transcribe the E1A gene and that insertion of an exogenous promoter downstream to the E1A regulatory region may not always disturb Ad replication.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2003.08.017