Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is expressed in several types of tissue. Although PPARγ reportedly is expressed in normal urothelium, its function is unknown. We examined the expression of PPARγ in normal urothelium and bladder cancer in an attempt to assess its functional role. Immunohistochemical staining revealed normal urothelium to express PPARγ 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 (1T1), a low-grade (RT4) carcinoma cell line, and two high-grade (T24 and 253J) carcinoma cell lines in culture expressed PPARγ mRNA and protein. Luciferase assay indicated that PPARγ was functional. PPARγ ligands (15-deoxy-Δ12,14-prostaglandin J2, 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 PPARγ or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPARγ ligands.
ASJC Scopus subject areas
- Pathology and Forensic Medicine