Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists.
Recent studies have demonstrated that peroxisome proliferator activator-receptors(PPAR)-gamma is expressed in various cancer tissues and its ligand induces growth arrest of these cancer cells through apoptosis. In our study, we investigated the expression of PPAR-alpha, beta and gamma in human bladder tumor (BT) and normal bladder (NB) tissues as well as the effects of PPAR-gamma ligands. Specimens were obtained from 170 patients with BT and 20 with NB. The expressions were investigated using RT-PCR and immunohistochemical methods. We also investigated the inhibitory effect of PPAR-gamma ligands on BT-derived cell line. Immunoreactive PPAR-alpha and -beta were significantly apparent in both BT and NB tissues. Although no marked expression of PPAR-gamma was observed in NB tissue, significant expression was found in BT tissue. The extent and intensity of immunoreactive PPAR-gamma polypeptides in BT cells were statistically much greater than those of NB cells. Correlation between PPAR-gamma expression and tissue type or progression of bladder cancer was observed; PPAR-gamma expression was higher in G3 of bladder cancer than in G1 and was higher in advanced than in early cancer. PPAR-gamma agonists, troglitazone and 15-deoxy-Delta(12, 14)-prostaglandin J(2) inhibited the growth of the BT cells. PPAR-gamma is expressed in bladder tumor, and results suggest that PPAR-gamma ligands may mediate potent antiproliferative effects against BT cells. Thus, PPAR-gamma has the ability to become a new target in treatment of bladder tumor.
Yoshimura
Rikio
R
Department of Urology, Osaka City University Medical School, Osaka, Japan. jasmin@med.osaka-cu.ac.jp
Matsuyama
Masahide
M
Segawa
Yoshihiro
Y
Hase
Taro
T
Mitsuhashi
Makoto
M
Tsuchida
Kennji
K
Wada
Seiji
S
Kawahito
Yutaka
Y
Sano
Hajime
H
Nakatani
Tatsuya
T
D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D000077288:Troglitazone; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
D002839:Chromans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone