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Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status

Cancer Gene Therapy volume 16, pages 832–840 (2009)Cite this article

Abstract

We examined cytotoxic effects of adenoviruses (Ad) expressing the p53 gene (Ad-p53) in nine human esophageal carcinoma cell lines with respect to the Ad receptor expression and the endogenous p53 gene status. Ad-p53-mediated cytotoxicity was related with an expression level of the coxsackievirus adenovirus receptor (CAR) but not with that of CD51, both of which are type 5 Ad receptors. Contrary to earlier studies, we found that the cytotoxicity was greater in tumor cells with the wild-type p53 gene than in those with mutated p53. The cytotoxic activity of Ad defective of E1B55kDa molecules (Ad-delE1B55), however, was not linked with the CAR expression level or the endogenous p53 status. We noticed that the tumor cells with the wild-type p53 gene showed greater CAR expression levels, although transduction with Ad-p53 did not upregulate the CAR expression in the mutated cells. We also examined the Ad-53-mediated cytotoxicity in two kinds of paired fibroblasts, parent and immortalized with loss of the p53 functions, and showed that the CAR expression level was more influential than the endogenous p53 status in the cytotoxicity. These data suggest that CAR expression level is a better predictive marker than endogenous p53 status for Ad-p53-mediated cytotoxicity in esophageal carcinoma.

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Acknowledgements

This study was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan and by a Grant-in-aid from the Nichias Corporation and the Futaba Electronics Memorial Foundation.

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Authors and Affiliations

  1. Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan

    G Ma, K Kawamura, Q Li & M Tagawa

  2. Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan

    G Ma & N Suzuki

  3. Shanghai Sunway Biotech Co. Ltd, Pudong, Shanghai, PR China

    M Liang

  4. Niimi College, Niimi, Okayama, Japan

    M Namba

  5. Division of Gastroenterological Surgery, Chiba Cancer Center, Chuo-ku, Chiba, Japan

    H Shimada

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  1. G Ma
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Correspondence to M Tagawa.

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Ma, G., Kawamura, K., Li, Q. et al. Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status. Cancer Gene Ther 16, 832–840 (2009). https://doi.org/10.1038/cgt.2009.21

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