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(American Journal of Pathology. 2001;159:591-597.)
© 2001 American Society for Investigative Pathology

Regular Articles

Role of Peroxisome Proliferator-Activated Receptor {gamma} and Its Ligands in Non-Neoplastic and Neoplastic Human Urothelial Cells

Koh-ichi Nakashiro, Yoshiki Hayashi, Akiyo Kita, Tetsuya Tamatani, Alexandre Chlenski, Nobuteru Usuda, Kazunori Hattori, Janardan K. Reddy and Ryoichi Oyasu

From the Department of Pathology, Northwestern University Medical School, Chicago, Illinois

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is expressed in several types of tissue. Although PPAR{gamma} reportedly is expressed in normal urothelium, its function is unknown. We examined the expression of PPAR{gamma} in normal urothelium and bladder cancer in an attempt to assess its functional role. Immunohistochemical staining revealed normal urothelium to express PPAR{gamma} 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 PPAR{gamma} mRNA and protein. Luciferase assay indicated that PPAR{gamma} was functional. PPAR{gamma} ligands (15-deoxy-{Delta}12,14-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 PPAR{gamma} or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPAR{gamma} ligands.




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