Differential susceptibility to TRAIL of normal versus malignant human urothelial cells

L. P. Steele, N. T. Georgopoulos, J. Southgate, P. J. Selby, L. K. Trejdosiewicz

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


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-κB. 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.

Original languageEnglish
Pages (from-to)1564-1576
Number of pages13
JournalCell Death and Differentiation
Issue number9
Early online date13 Jan 2006
Publication statusPublished - 1 Sep 2006
Externally publishedYes


Dive into the research topics of 'Differential susceptibility to TRAIL of normal versus malignant human urothelial cells'. Together they form a unique fingerprint.

Cite this