Fig. 1.

Induction of key tumor suppressors in ‘simple urothelial hyperplasia’ elicited by constitutively active Ha-ras. (A) Hematoxylin and eosin-stained cross sections of bladder urothelia of a 6-month-old wild-type (WT) mouse and five heterozygous UPII/Ha-ras* transgenic mice (1, 2, 4, 6 and 9 months of age) expressing a constitutively active Ras oncogene (Ras*) in the urothelium. Note the persistent urothelial hyperplasia and lack of tumorigenesis irrespective of the age. All panels are ×200. (B and C) Urothelial responses to hyperproliferation. Real-time quantitative PCR (B) and western blotting (C) show marked induction of tumor suppressor genes including those in the p53 pathway (e.g. p19, p53, p21) and those in the pRb pathway (e.g. p16, pRb, p107, p130). Values were means ± SD. N = 8 mice per genotype and per gene analyzed in (B) and N = 3 per genotype in (C).