Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is expressed in several types of tissue. Although PPARgamma reportedly is expressed in normal urothelium, its function is unknown. We examined the expression of PPARgamma in normal urothelium and bladder cancer in an attempt to assess its functional role. Immunohistochemical staining revealed normal urothelium to express PPARgamma uniformly. All low-grade carcinomas were positive either diffusely or focally, whereas staining was primarily focal or absent in high-grade carcinomas. A nonneoplastic urothelial cell line (1T-1), a low-grade (RT4) carcinoma cell line, and two high-grade (T24 and 253J) carcinoma cell lines in culture expressed PPARgamma mRNA and protein. Luciferase assay indicated that PPARgamma was functional. PPARgamma ligands (15-deoxy-Delta(12,14)-prostaglandin J(2), troglitazone and pioglitazone) suppressed the growth of nonneoplastic and neoplastic urothelial cells in a dose-dependent manner. However, neoplastic cells were more resistant than were nonneoplastic cells. Failure to express PPARgamma or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPARgamma ligands.

The Nakano Cataract (NCT) is an autosomal, recessive, single gene mutation in mice leading to an osmotic cataract induced by an endogenous inhibitor of Na, K-ATPase. In this report, we further refined the map position of the mutant locus to a <0.7c M segment between D16Mit5 and D16Mit185 in 1,000 BALB/c-nct/nct x(BALB/c- nct/nctxMSM)F1 backcrossed mice with PCR-based microsatellite analysis. The NCT in the original Nakano mice developed at 3 weeks of age, rapidly formed a pin-head type dense opacity, whereas the cataract in the congenic BALB/c- nct/nct mice developed at 5-6 weeks of age or later, slowly formed a diffuse opacity. A major histological difference was the presence or absence of heavy condensation of the lens nucleus. These two types of cataract were segregated in the backcrossed mice. Linkage analysis of the two subtypes among the backcrossed mice revealed two recessive BALB/c-derived modifier genes on chromosome 3 and 10.