| Carrier cell-mediated cell lysis of squamous cell carcinoma cells by squamous cell carcinoma antigen 1 promoter-driven oncolytic adenovirus. | |
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MedLine Citation:
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PMID: 20527047 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes: SCCA1 and SCCA2. SCCA1 gene is up-regulated in squamous cell carcinoma cells. We analyzed the proximal region of the SCCA1 promoter and the antitumor effect of oncolytic adenovirus driven by the SCCA1 promoter in squamous cell carcinoma cells. METHODS: The SCCA1 promoter was analyzed by dual luciferase assay and substituted with the E1A promoter to construct the oncolytic adenovirus to determine the squamous cell carcinoma-specific cell lysis. RESULTS: Deletion analysis of SCCA1 promoter identified a 175-bp core promoter region and an enhancer region at -525 to -475 bp upstream of the transcription start site. The transcriptional activity of the SCCA1 promoter was up-regulated in squamous cell carcinoma cells. Five tandem repeats of enhancer increased SCCA1 promoter activity by four-fold. Oncolytic adenovirus driven by this SCCA1 enhancer-promoter complex specifically killed squamous cell carcinoma cells in vitro and in vivo. A549 carrier cells infected with the oncolytic adenovirus induced complete regression of syngeneic squamous cell carcinoma cell tumor by overcoming immunogenicity and adenovirus-mGM-CSF augmented the antitumor effect of carrier cells. CONCLUSIONS: SCCA1 was up-regulated in squamous cell carcinoma cells and oncolytic adenovirus driven by SCCA1 promoter specifically killed these cells. These findings suggest that SCCA1 promoter is a potential target of gene therapy for squamous cell carcinoma. |
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Authors:
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Katsuyuki Hamada; Ting Zhang; Junzo Desaki; Koh-ichi Nakashiro; Hiroshi Itoh; Kenzaburo Tani; Yoshiyuki Koyama; Hiroyuki Hamakawa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journal of gene medicine Volume: 12 ISSN: 1521-2254 ISO Abbreviation: J Gene Med Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-07 Completed Date: 2010-10-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: England |
Other Details:
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Languages: eng Pagination: 545-54 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. hamakatu@m.ehime-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae*
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genetics,
metabolism Animals Antigens, Neoplasm / genetics* Carcinoma, Squamous Cell / genetics*, pathology, therapy* Cell Death Cell Line, Tumor Cell Proliferation Gene Therapy / methods Humans Mice Mice, Nude Oncolytic Virotherapy / methods* Oncolytic Viruses* / genetics, metabolism Promoter Regions, Genetic* Protein Isoforms / genetics, metabolism RNA, Messenger / genetics, metabolism Serpins / genetics* Survival Rate Tumor Markers, Biological / genetics |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Neoplasm; 0/Protein Isoforms; 0/RNA, Messenger; 0/Serpins; 0/Tumor Markers, Biological; 0/squamous cell carcinoma-related antigen |
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