title: A novel gene expression system strongly enhances the anticancer effects of a REIC/Dkk-3-encoding adenoviral vector.
abstract: 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.
authors.affiliation: Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Cell Biology, Okayama University, Okayama, Japan.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Department of Medical and Bioengineering Science, Okayama University, Okayama, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kinoshita
authors.affiliation: Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kaku
authors.affiliation: Department of Urology, Okayama University, Okayama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ariyoshi
authors.affiliation: Department of Urology, Okayama University, Okayama, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueki
authors.affiliation: Department of Urology, Okayama University, Okayama, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Tanimoto
authors.affiliation: Department of Urology, Okayama University, Okayama, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ebara
authors.affiliation: Department of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Department of Medical and Bioengineering Science, Okayama University, Okayama, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Futami
authors.affiliation: Department of Urology, Okayama University, Okayama, Japan.
authors.forename: Shun-Ai
authors.initials: SA
authors.lastname: Li
authors.affiliation: Department of Urology, Okayama University, Okayama, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.affiliation: Department of Cell Biology, Okayama University, Okayama, Japan.
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
authors.affiliation: Department of Urology, Okayama University, Okayama, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D018925:Chemokines; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D047368:Tumor Burden
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins