p53 Mutation in Bladder Cancer Patients in Japan and Inhibition of Growth by in Vitro Adenovirus-Mediated Wild-Type p53 Transduction in Bladder Cancer Cells

Abstract

Background

: Altered expression of p53 has been described in nearly half of bladder cancers, and p53 mutations are presumed to play a role in the multistep progression of these tumors.

Materials and Methods

: The incidence of mutation in the p53 gene and its correlation with histopathologic findings and patient survival were evaluated in 105 Japanese patients with bladder cancer. Laboratory experiments were also performed to confirm the infectivity and efficacy in tumor growth inhibition of an adenovirus expressing wild-type p53 in EJ bladder cancer cells.

Results

: Mutations of p53 were observed in 38 bladder cancer specimens (36%), with a significantly higher incidence of mutation being seen in tumors of higher stage and grade. The overall survival was worse in patients with the p53 mutation. In laboratory experiments, adenoviral vectors infected bladder cancer cells in a dose- and cell density-dependent manner. The adenovirus-mediated transduction of wild-type p53 resulted in dose-dependent growth inhibition of bladder cancer cells in vitro. No significant cytotoxicity was observed after infection by a control adenovirus.

Conclusion

: Transduction of wild-type p53 might be a potential therapeutic option for bladder cancer.