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S100A2 promoter-driven conditionally replicative adenovirus targets non-small-cell lung carcinoma

Title
S100A2 promoter-driven conditionally replicative adenovirus targets non-small-cell lung carcinoma
Author
윤채옥
Keywords
S100A2 promoter; epidermal growth factor receptor signaling; conditionally replicative adenovirus; non-small-cell lung carcinoma
Issue Date
2012-10
Publisher
NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Citation
Gene Therapy, Vol.19, No.10 [2012], p967-977
Abstract
S100A2, a member of the S100 family of calcium-binding proteins, has been implicated in carcinogenesis as both a tumor suppressor and stimulator. Here, we characterized promoter activity of S100A2, generated an S100A2 promoter-driven conditionally replicative adenovirus (Ad/SA), and evaluated its anti-tumor activity in vitro and in vivo. Promoter activity of S100A2 was greatly restricted to tumor cells, and the S100A2 promoter bound with typical nuclear targets of epidermal growth factor receptor (EGFR) signaling. EGF-stimulated EGFR phosphorylation induced S100A2 expression and further activated E1A expression of Ad/SA, which was restored by EGFR signal inhibition in a concentration-dependent manner in non-small-cell lung carcinoma (NSCLC). In two EGFR-activated tumor xenograft animal models, Ad/SA exhibited potent anti-tumor activity, whereas cetuximab, an EGFR-targeting anticancer drug, was active transiently or ineffective. Combined treatment with cetuximab or cisplatin plus Ad/SA resulted in enhanced anti-tumor activity. Immunohistochemical analysis of tumor sections showed moderate-to-high grade signals for EGFR and adenovirus, and a reduction in viable cells in Ad/SA-treated tumors. Collectively, these results demonstrate that the S100A2 promoter-driven adenovirus is a potent inhibitor of cancers, and further suggest that S100A2 is a target gene of EGFR signaling pathway in NSCLC.
URI
https://www.nature.com/articles/gt2011168http://hdl.handle.net/20.500.11754/39695
ISSN
0969-7128
DOI
10.1038/gt.2011.168
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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