1. ¹Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan
2. ²Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
3. ³Shanghai Sunway Biotech Co. Ltd, Pudong, Shanghai, PR China
4. ⁴Niimi College, Niimi, Okayama, Japan
5. ⁵Division of Gastroenterological Surgery, Chiba Cancer Center, Chuo-ku, Chiba, Japan

Correspondence: Dr M Tagawa, Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan. E-mail: mtagawa@chiba-cc.jp

Received 16 September 2008; Revised 28 November 2008; Accepted 24 January 2009; Published online 10 April 2009.

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.