論文

査読有り
2017年9月

Cytotoxicity of replication-competent adenoviruses powered by an exogenous regulatory region is not linearly correlated with the viral infectivity/gene expression or with the E1A-activating ability but is associated with the p53 genotypes

BMC CANCER
  • Suguru Yamauchi
  • ,
  • Boya Zhong
  • ,
  • Kiyoko Kawamura
  • ,
  • Shan Yang
  • ,
  • Shuji Kubo
  • ,
  • Masato Shingyoji
  • ,
  • Ikuo Sekine
  • ,
  • Yuji Tada
  • ,
  • Koichiro Tatsumi
  • ,
  • Hideaki Shimada
  • ,
  • Kenzo Hiroshima
  • ,
  • Masatoshi Tagawa

17
1
開始ページ
622
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/s12885-017-3621-x
出版者・発行元
BIOMED CENTRAL LTD

Background: Replication-competent adenoviruses (Ad) produced cytotoxic effects on infected tumors and have been examined for the clinical applicability. A biomarkers to predict the cytotoxicity is valuable in a clinical setting.
Methods: We constructed type 5 Ad (Ad5) of which the expression of E1A gene was activated by a 5' regulatory sequences of survivin, midkine or cyclooxygenase-2, which were highly expressed in human tumors. We also produced the same replication-competent Ad of which the fiber-knob region was replaced by that of Ad35 (AdF35). The cytotoxicity was examined by a colorimetric assay with human tumor cell lines, 4 kinds of pancreatic, 9 esophageal carcinoma and 5 mesothelioma. Ad infectivity and Ad-mediated gene expression were examined with replication-incompetent Ad5 and AdF35 which expressed the green fluorescence protein gene. Expression of cellular receptors for Ad5 and AdF35 was also examined with flow cytometry. A transcriptional activity of the regulatory sequences was investigated with a luciferase assay in the tumor cells. We then investigated a possible correlation between Ad-mediated cytotoxicity and the infectivity/gene expression, the transcriptional activity or the p53 genotype.
Results: We found that the cytotoxicity was greater with AdF35 than with Ad5 vectors, but was not correlated with the Ad infectivity/gene expression irrespective of the fiber-knob region or the E1A-activating transcriptional activity. In contrast, replication-competent Ad produced greater cytotoxicity in p53 mutated than in wild-type esophageal carcinoma cells, suggesting a possible association between the cytotoxicity and the p53 genotype.
Conclusions: Sensitivity to Ad-mediated cytotoxic activity was linked with the p53 genotype but was not lineally correlated with the infectivity/gene expression or the E1A expression.

Web of Science ® 被引用回数 : 2

リンク情報
DOI
https://doi.org/10.1186/s12885-017-3621-x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28874135
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000409193300005&DestApp=WOS_CPL

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