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Research Paper
Interferon-α Induces TRAIL Expression and Cell Death Via an IRF-1-Dependent Mechanism in Human Bladder Cancer Cells
Angela Papageorgiou, Colin P.N. Dinney and David J. McConkey
volume 6 | issue 6
June 2007We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
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Apoptosis induced by interferon-alpha (IFNα) is associated with induction of TRAIL in a number of different cell types. Here we examined whether or not TRAIL was required for apoptosis in a model human bladder cancer cell line (UM-UC-12) and defined the molecular mechanisms involved in IFNα-induced TRAIL expression. Exposure to IFNα resulted in concentration-dependent induction of TRAIL and apoptosis. Inhibition of TRAIL or downstream components of the TRAIL cell death pathway (FADD, caspase-8) via siRNA-mediated knockdown attenuated IFNα-induced cell death, thereby implicating TRAIL in the response. IFNα induced rapid STAT-1 phosphorylation and DNA binding activity and subsequent accumulation of IRF-1. Transfection with siRNAs directed against STAT-1 or IRF-1 inhibited IFNα-induced TRAIL production and cell death, and chromatin immunprecipitation (ChIP) analyses demonstrated that IFNα induced direct, time-dependent binding of both transcription factors to the TRAIL promoter. Together, our results demonstrate that IFNα induces TRAIL expression via a STAT-1/IRF-1-dependent mechanism in human bladder cancer cells, and this induction of TRAIL plays an important role in IFNα-induced cell killing.
Authors
Angela Papageorgiou
U.T. M.D. Anderson Cancer Center, Houston, TX
Colin P.N. Dinney
U.T. M.D. Anderson Cancer Center, Houston, TX
David J. McConkey
Department of Cancer, University of Texas M.D. Anderson Cancer Center
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.