A experimental model of bladder cancer using nonviral vector expressing uroplakin II promoter and SV40 T antigen

Purpose: The goal of this study was to constructing a nonviral vector, expressing the chimeric gene of the SV40 T antigen and mouse uroplakin II promoter (UPII promotor), which was uniquely expressed in the urothelium, to aid in the treatment of bladder cancer by the creation of a tumor that will express itself in the bladder only, but that will have no effect on the other urothelium. Materials and methods: 36 female C3H/He mice, weighing 20-25grams, were used in this study. A UPII-GFP-liposome complex was installed into the bladder, with Enhanced Green Fluorescent Protein (EGFP), expressing the bladder mucosa, and analyzed via fluorescent microscopy. A UPII-SV40T-liposome complex was then administered into the bladders of the mice, and the bladder and ureter examined, grossly and microscopically, at 1, 2, 3 and 4 weeks, to find transitional cell carcinomas specific to the bladder, the degree of bladder cancer development, and whether the development was from superficial to deep tumors, as well as tumor metastasis. Results: The expression of EGFP was found in all four mice after 2 days. No development of tumors was evident in any mice. However, of the 6 mice sacrificed 28 days after bladder instillation, urothelial dysplasia was evident in 4. There was no evidence of transient cell carcinomas in the ureter or renal pelvis in any of the mice, or of distant metastasis during the term of the study. Conclusions: This model of bladder cancer seems to take longer than other models for cancer formation as the carcinogen affects the DNA of urothelial cell for the formation of bladder cancer. However, our bladder cancer model was better than others due to its similarity for the processes of normal bladder cancer formation.