PMID- 16397226
OWN - NLM
STAT- MEDLINE
DCOM- 20060223
LR  - 20220408
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 1
DP  - 2006 Jan 1
TI  - Thioredoxin-1 modulates transcription of cyclooxygenase-2 via hypoxia-inducible 
      factor-1alpha in non-small cell lung cancer.
PG  - 143-50
AB  - Hypoxic induction of gene expression occurs mainly via the hypoxia-inducible 
      factor-1 (HIF-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-1alpha 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-1alpha to induce 
      hypoxia-responsive genes under normoxic conditions. Our results identify two new 
      mechanisms for regulation of COX-2 expression in NSCLC.
FAU - Csiki, Ildiko
AU  - Csiki I
AD  - Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Nashville, 
      Tennessee 37232-6838, USA.
FAU - Yanagisawa, Kiyoshi
AU  - Yanagisawa K
FAU - Haruki, Nobuhiro
AU  - Haruki N
FAU - Nadaf, Sorena
AU  - Nadaf S
FAU - Morrow, Jason D
AU  - Morrow JD
FAU - Johnson, David H
AU  - Johnson DH
FAU - Carbone, David P
AU  - Carbone DP
LA  - eng
GR  - CA076321/CA/NCI NIH HHS/United States
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - CA77839/CA/NCI NIH HHS/United States
GR  - CA90949/CA/NCI NIH HHS/United States
GR  - DK48831/DK/NIDDK NIH HHS/United States
GR  - GM15431/GM/NIGMS NIH HHS/United States
GR  - K24CA080908/CA/NCI NIH HHS/United States
GR  - RR00095/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/enzymology/genetics/*metabolism/pathology
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Cyclooxygenase 2/*biosynthesis/genetics
MH  - Enzyme Induction
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/pharmacology/*physiology
MH  - Lung Neoplasms/enzymology/genetics/*metabolism/pathology
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Thioredoxins/*biosynthesis/genetics
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
EDAT- 2006/01/07 09:00
MHDA- 2006/02/24 09:00
CRDT- 2006/01/07 09:00
PHST- 2006/01/07 09:00 [pubmed]
PHST- 2006/02/24 09:00 [medline]
PHST- 2006/01/07 09:00 [entrez]
AID - 66/1/143 [pii]
AID - 10.1158/0008-5472.CAN-05-1357 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Jan 1;66(1):143-50. doi: 10.1158/0008-5472.CAN-05-1357.