Role of peroxisome proliferator-activated receptor γ and its ligands in non-neoplastic and neoplastic human urothelial cells
Role of peroxisome proliferator-activated receptor γ and its ligands in non-neoplastic and neoplastic human urothelial cells
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DOI：
10.1016/s0002-9440(10)61730-0
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发表时间：
2001-08-01
影响因子：
6
通讯作者：
Oyasu, R
中科院分区：
文献类型：
--
作者：
Nakashiro, K;Hayashi, Y;Oyasu, R
过氧化物酶体增殖体激活受体γ (ppar - γ)是配体激活转录因子核受体超家族的成员，在多种组织中表达。尽管据报道PPAR γ在正常尿路上皮中表达，但其功能尚不清楚。我们检测了PPAR γ在。正常尿路上皮和膀胱癌的功能作用。免疫组化染色显示正常尿路上皮均匀表达PPAR γ。所有低级别癌均为弥漫性或局灶性阳性，而高级别癌主要为局灶性或无染色。一个非肿瘤性尿路上皮细胞系（1T-1）、一个低级别（RT4）癌细胞系和两个高级别（T24和253J）癌细胞系在培养中表达PPAR γ mRNA和蛋白。荧光素酶测定表明PPAR γ具有功能性。PPAR γ配体(15-脱氧- δ（12,14)-前列腺素J(2)、曲格列酮和吡格列酮）以剂量依赖性方式抑制非肿瘤性和肿瘤性尿路上皮细胞的生长。然而，肿瘤细胞比非肿瘤细胞更具耐药性。未能表达PPAR γ或转录活性无效可能是PPAR γ配体抑制作用的一些机制。
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 fine, 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 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 PPAR gamma or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPAR gamma ligands.