Transcriptional control of viral gene therapy by cisplatin
AUTOR(ES)
Park, James O.
FONTE
American Society for Clinical Investigation
RESUMO
Ionizing radiation (IR) and radical oxygen intermediates (ROIs) activate the early growth response-1 (Egr1) promoter through specific cis-acting sequences termed CArG elements. Ad.Egr.TNF.11D, a replication-deficient adenoviral vector containing CArG elements cloned upstream of the cDNA for human recombinant TNF-α was used to treat human esophageal adenocarcinoma and rat colon adenocarcinoma cells in culture and as xenografts in athymic nude mice. Cisplatin, a commonly used chemotherapeutic agent, causes tumor cell death by producing DNA damage and generating ROIs. The present studies demonstrate induction of TNF-α production in tumor cells and xenografts treated with the combination of Ad.Egr.TNF.11D and cisplatin. The results show that the Egr1 promoter is induced by cisplatin and that this induction is mediated in part through the CArG elements. These studies also demonstrate an enhanced antitumor response without an increase in toxicity following treatment with Ad.Egr.TNF.11D and cisplatin, compared with either agent alone. Chemo-inducible cancer gene therapy thus provides a means to control transgene expression while enhancing the effectiveness of commonly used chemotherapeutic agents.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=151093Documentos Relacionados
- E1A control of gene expression is mediated by sequences 5' to the transcriptional starts of the early viral genes.
- Control of adenovirus early gene expression: posttranscriptional control mediated by both viral and cellular gene products.
- Transcriptional control of the Saccharomyces cerevisiae PGK gene by RAP1.
- Transcriptional control of the yeast PDR5 gene by the PDR3 gene product.
- Transcriptional Targeting in Cancer Gene Therapy
