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Differential susceptibility to TRAIL of normal versus malignant human urothelial cells

Steele, Lynette P., Georgopoulos, Nikolaos T., Southgate, Jennifer, Selby, Peter J. and Trejdosiewicz, Ludwik K. (2006) Differential susceptibility to TRAIL of normal versus malignant human urothelial cells. Cell Death and Differentiation, 13 (9). pp. 1564-1576. ISSN 1350-9047

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Comparing normal human urothelial (NHU) cells to a panel of six representative urothelial cell carcinoma (UCC)-derived cell lines, we showed that while TRAIL receptor expression patterns were similar, susceptibility to soluble recombinant crosslinked TRAIL fell into three categories. 4/6 carcinoma lines were sensitive, undergoing rapid and extensive death; NHU and 253J cells were partially resistant and HT1376 cells, like normal fibroblasts, were refractory. Both normal and malignant urothelial cells underwent apoptosis via the same caspase-8/9-mediated mechanism. Rapid receptor downregulation was a mechanism for evasion by some UCC cells. TRAIL resistance in malignant urothelial cells was partially dependent on FLIPL and was differentially mediated by p38MAPK, whereas in normal cells, resistance was mediated by NF-B. Importantly, extensive killing of UCC cells could be induced using noncrosslinked TRAIL after prolonged exposure, with no damage to their homologous, normal urothelial cell counterparts.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Schools: School of Applied Sciences
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Depositing User: Cherry Edmunds
Date Deposited: 01 Dec 2009 15:16
Last Modified: 28 Aug 2021 10:53


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