Regulation of cell proliferation by induction of p21/WAF1 in rat bladder carcinoma cells using the Cre–loxP system

p21/WAF1, a cyclin-dependent kinase inhibitory protein, functions as a tumor suppressor. Loss of p21/WAF1 expression has been reported to be an important prognostic predictor in several human malignancies, including bladder carcinomas. In this study, we induced p21/WAF1 using a Cre–loxP gene expression switching vector system in BC31 rat bladder carcinoma cells that feature p53 gene mutations. Cells in which p21/WAF1 was induced in nuclei were not labeled with BrdU and overall showed decreased cell proliferation, with increase in the G0–G1 population evident on flow cytometer analysis. The Cre treatment did not affect BC31 parental cells. These results show induction of p21/WAF1 can inhibit proliferation of tumor cells having p53 mutations, and could thus be applied as a potential therapy.