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Carrier cell-mediated cell lysis of squamous cell carcinoma by squamous cell carcinoma antigen 1 promoter-driven oncolytic adenovirus

Katsuyuki Hamada¹, Ting Zhang¹, Junzo Desaki¹, Koh-ichi Nakashiro¹, Hiroshi Ito², Kenzaburo Tani³, Yoshiyuki Koyama⁴ & Hiroyuki Hamakawa¹

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1. Ehime University, Japan
2. Tokyo University of Agriculture and Technology, Japan
3. Kyushu University, Japan
4. Otsuma Women's University, Japan

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Document Type:

Manuscript

Date:

Received 02 May 2009 09:34 UTC; Posted 08 May 2009

Subjects:

Cancer

Tags:

• carcinoma
• promoter
• squamous cell carcinoma antigen 1
• cervical cancer
• oncolytic adenovirus
• carrier cell
• SCCA

Abstract:

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. We examined the promoter activity of the 5'-flanking proximal region of the SCCA1 gene. 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, compared with normal keratinocyte, normal non-keratinocyte and adenocarcinoma cells. Five tandem repeats of enhancer increased SCCA1 promoter activity by 4-fold. Oncolytic adenovirus driven by the SCCA1 promoter with 5 tandem repeats of enhancer specifically killed squamous cell carcinoma cells in vitro and in vivo. A549 carrier cells infected with the oncolytic adenovirus induced complete regression of tumor by overcoming immunogenicity and adenovirus-mGM-CSF augmented the antitumor effect of carrier cells. These findings suggest that SCCA1 promoter is a potential target of gene therapy for squamous cell carcinoma.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Hamada, Katsuyuki, Zhang, Ting, Desaki, Junzo, Nakashiro, Koh-ichi, Ito, Hiroshi, Tani, Kenzaburo, Koyama, Yoshiyuki, and Hamakawa, Hiroyuki. Carrier cell-mediated cell lysis of squamous cell carcinoma by squamous cell carcinoma antigen 1 promoter-driven oncolytic adenovirus. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3213.1> (2009)

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