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, David McConkey

Research output: Contribution to journalArticle

Abstract

Apoptosis induced by interferon-alpha (IFNa) 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. IFNαinduced 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.

Original languageEnglish (US)
Pages (from-to)872-879
Number of pages8
JournalCancer Biology and Therapy
Volume6
Issue number6
Publication statusPublished - Jun 2007
Externally publishedYes

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Keywords

  • Caspase-8
  • ChIP
  • FADD
  • siRNA
  • UM-UC-12

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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