A novel gene expression system strongly enhances the anticancer effects of a REIC/Dkk-3-encoding adenoviral vector
| Autor: | Ryuta Tanimoto, Yuichi Ariyoshi, Shun Ai Li, Kazuhiko Ochiai, Hiromi Kumon, Masami Watanabe, Hideo Ueki, Haruki Kaku, Yasutomo Nasu, Nam Ho Huh, Junichiro Futami, Shin Ebara, Peng Huang, Rie Kinoshita, Masakiyo Sakaguchi |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Genetic enhancement Genetic Vectors Gene Expression Mice Nude Apoptosis Biology Simian virus 40 enhancer Adenoviridae Viral vector Mice Neoplasms Gene expression Animals Humans Telomerase reverse transcriptase Gene Adaptor Proteins Signal Transducing Mice Inbred BALB C Oncogene HEK 293 cells Genetic Therapy Articles adenovirus General Medicine human telomerase reverse transcriptase enhancer Molecular biology Tumor Burden HEK293 Cells Oncology cytomegalovirus enhancer Cancer research Intercellular Signaling Peptides and Proteins Female Expression cassette Chemokines Neoplasm Transplantation HeLa Cells |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2013.2958 |
| Popis: | Gene expression systems with various promoters, including the cytomegalovirus (CMV) promoter, have been developed to increase the gene expression in a variety of normal and cancer cells. In particular, in the clinical trials of cancer gene therapy, a more efficient and robust gene expression system is required to achieve sufficient therapeutic outcomes. By inserting the triple translational enhancer sequences of human telomerase reverse transcriptase (hTERT), Simian virus 40 (SV40) and CMV downstream of the sequence of the BGH polyA, we were able to develop a novel gene expression system that significantly enhances the expression of the genes of interest. We termed this novel gene expression cassette the super gene expression (SGE) system, and herein verify the utility of the SGE cassette for a replication-deficient adenoviral vector. We newly developed an adenoviral vector expressing the tumor suppressor, reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), based on the CMV promoter-driven SGE system (Ad-SGE-REIC) and compared the therapeutic utility of Ad-SGE-REIC with that of the conventional adenoviral vectors (Ad-CMV-REIC or Ad-CAG-REIC). The results demonstrated that the CMV promoter-SGE system allows for more potent gene expression, and that the Ad-SGE-REIC is superior to conventional adenoviral systems in terms of the REIC protein expression and therapeutic effects. Since the SGE cassette can be applied for the expression of various therapeutic genes using various vector systems, we believe that this novel system will become an innovative tool in the field of gene expression and gene therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|