Document Detail

Carrier cell-mediated cell lysis of squamous cell carcinoma cells by squamous cell carcinoma antigen 1 promoter-driven oncolytic adenovirus.
MedLine Citation:
PMID:  20527047     Owner:  NLM     Status:  MEDLINE    
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.
Katsuyuki Hamada; Ting Zhang; Junzo Desaki; Koh-ichi Nakashiro; Hiroshi Itoh; Kenzaburo Tani; Yoshiyuki Koyama; Hiroyuki Hamakawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The journal of gene medicine     Volume:  12     ISSN:  1521-2254     ISO Abbreviation:  J Gene Med     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-10-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  545-54     Citation Subset:  IM    
Department of Obstetrics and Gynecology, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
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MeSH Terms
Adenoviridae* / genetics,  metabolism
Antigens, Neoplasm / genetics*
Carcinoma, Squamous Cell / genetics*,  pathology,  therapy*
Cell Death
Cell Line, Tumor
Cell Proliferation
Gene Therapy / methods
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
Reg. No./Substance:
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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