Expression of peroxisome proliferator-activated receptor gamma in renal cell carcinoma and growth inhibition by its agonists.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorgenesis. Up-date, the up-regulation of PPAR-gamma expression is a frequent occurrence in a variety of different malignant tumors. In this study, we investigated the expression of PPAR-gamma in human renal cell carcinoma (RCC) tissues, and the role of PPAR-gamma in cell growth in human RCC-derived cell lines. Immunohistochemistry showed a strong immunoreactive expression of PPAR-gamma in all slides from cancer specimens. RT-PCR and Western blot analysis showed 3 RCC cell lines expressed PPAR-gamma mRNA and its protein. MTT assay in 3 RCC cells showed that the synthetic PPAR-gamma agonists thiazolidinedione compounds (pioglitazone and troglitazone) and the endogeneous PPAR-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J(2) (15dPGJ(2)) inhibited the growth of the RCC cells. These results suggest that PPAR-gamma may become a new target in the treatment of RCC.
Inoue
K
K
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi, Kamigyouku, Kyoto, 602-0841, Japan.
Kawahito
Y
Y
Tsubouchi
Y
Y
Kohno
M
M
Yoshimura
R
R
Yoshikawa
T
T
Sano
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002455:Cell Division; D002839:Chromans / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000378:metabolism*; D008024:Ligands; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000970:Antineoplastic Agents; D002839:Chromans; D004396:Coloring Agents; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013778:Tetrazolium Salts; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione; C022616:thiazolyl blue; D000077288:Troglitazone; D015230:Prostaglandin D2; D000077205:Pioglitazone