RB1 and neoplasm: In direct support of our tumor-defense line of reasoning, functional inactivation of both p16-pRB and p19-p53-p21 pathways by urothelial expression of SV40 large T antigen induced high-grade papillary urothelial carcinoma of the bladder (HGP-UCB) in double transgenic mice that simultaneously expressed the FGFR3b mutant in the urothelium (Figs 3, 4, 5, 6).