An hTERT-immortalized human urothelial cell line that responds to anti-proliferative factor

An hTERT-immortalized human urothelial cell line that responds to anti-proliferative factor
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DOI:
10.1007/s11626-010-9350-y
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发表时间:
2011-01-01
影响因子:
2.1
通讯作者:
Adam, Rosalyn M.
Adam, Rosalyn M.
中科院分区:
生物学4区
文献类型:
--
作者:
Kim, Jayoung;Ji, Mihee;Adam, Rosalyn M.

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尿路上皮是膀胱的专门上皮衬里,研究尿路上皮对于了解影响下尿路的疾病至关重要,包括间质性膀胱炎、尿路感染和癌症。然而,我们对尿路上皮病理生理学的理解一直受到缺乏适当的模型系统。在这里,我们描述了一个非转化的尿路上皮细胞系(TRT-HU 1)的分离和表征,最初从正常组织中分离出来,用端粒酶的催化亚基hTERT永生化。我们证明了细胞对抗增殖因子(APF)的反应,APF是一种与间质性膀胱炎发病机制有关的糖肽。TRT-HU 1携带9号染色体短臂上的缺失,这是膀胱癌发展中的早期遗传病变。TRT-HU 1尿路上皮细胞显示出与低度乳头状瘤细胞系RT 4相似的生长和迁移特性。相反,我们观察到TRT-HU 1和高度恶性的T24细胞系之间的表型和基因表达谱的显着差异。总之,这些发现首次证明了对APF有反应的非转化的连续尿路上皮细胞系。该细胞系对良性和恶性尿路上皮细胞生物学的研究具有重要价值。
Studies of the urothelium, the specialized epithelial lining of the urinary bladder, are critical for understanding diseases affecting the lower urinary tract, including interstitial cystitis, urinary tract infections and cancer. However, our understanding of urothelial pathophysiology has been hampered by a lack of appropriate model systems. Here, we describe the isolation and characterization of a non-transformed urothelial cell line (TRT-HU1), originally explanted from normal tissue and immortalized with hTERT, the catalytic subunit of telomerase. We demonstrate responsiveness of the cells to anti-proliferative factor (APF), a glycopeptide implicated in the pathogenesis of interstitial cystitis. TRT-HU1 carries a deletion on the short arm of chromosome 9, an early genetic lesion in development of bladder cancer. TRT-HU1 urothelial cells displayed growth and migration characteristics similar to the low-grade papilloma cell line RT4. In contrast, we observed marked differences in both phenotype and gene expression profiles between TRT-HU1 and the highly malignant T24 cell line. Together, these findings provide the first demonstration of a non-transformed, continuous urothelial cell line that responds to APF. This cell line will be valuable for studies of both benign and malignant urothelial cell biology.