Thioredoxin-1 modulates transcription of cyclooxygenase-2 via hypoxia-inducible factor-1α in non-small cell lung cancer

Ildiko Csiki, Kiyoshi Yanagisawa, Nobuhiro Haruki, Sorena Nadaf, Jason D. Morrow, David H. Johnson, David P. Carbone

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Hypoxic induction of gene expression occurs mainly via the hypoxia-inducible factor-1 (HIP-1) transcription factor and is a critical step in tumor growth. Cyclooxygenase-2 (COX-2) is commonly overexpressed in non-small cell lung cancer (NSCLC). In this study, we sought to determine the role of HIF-1 in the induction of COX-2 expression during hypoxia. Through sequence comparison of hypoxia-responsive genes, COX-2 promoter deletion analysis, and site-directed mutagenesis, we identified a hypoxia-responsive element within the COX-2 promoter that interacts with HIF-1α and underlies the mechanism of hypoxic activation of COX-2 in lung cancer cells. Proteomic analysis of NSCLC identified thioredoxin-1 as a redox protein overexpressed in NSCLC correlated with poor prognosis. We also show that thioredoxin-1 stabilizes HIF-1α to induce hypoxia-responsive genes under normoxic conditions. Our results identify two new mechanisms for regulation of COX-2 expression in NSCLC.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalCancer Research
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Thioredoxin-1 modulates transcription of cyclooxygenase-2 via hypoxia-inducible factor-1α in non-small cell lung cancer'. Together they form a unique fingerprint.

  • Cite this