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.