PMID- 21119667
OWN - NLM
STAT- MEDLINE
DCOM- 20110215
LR  - 20211130
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 104
IP  - 1
DP  - 2011 Jan 4
TI  - A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear 
      factor-kappaB promotes gastric tumour growth and angiogenesis.
PG  - 166-74
LID - 10.1038/sj.bjc.6606020 [doi]
AB  - BACKGROUND: The underlying mechanisms involved in the activation of 
      hypoxia-inducible factor-1 (HIF-1) in gastric cancer remain unclear. As nuclear 
      factor-kappaB (NF-kappaB) as well as HIF-1 have been implicated in angiogenesis of 
      various cancers, we investigated their relationship in gastric cancer. METHODS: 
      Nuclear expressions of HIF-1alpha and NF-kappaB/RelA were assessed in 251 human gastric 
      carcinoma specimens by immunohistochemical tissue array analysis. Stable human 
      gastric cancer cells, infected with a retroviral vector containing 
      super-suppressive mutant form of IkappaBalpha (IkappaBalphaM), were used for animal studies as 
      well as cell culture experiments. Xenografted tumours were measured and IkappaBalphaM 
      effects on angiogenesis and HIF-1alpha activation were assessed by 
      immunohistochemistry, western blotting, luciferase reporter assay, and 
      semiquantitative reverse transcription-polymerase chain reaction. In addition, 
      NF-kappaB effects on the HIF-1alpha degradation and synthesis were examined. RESULTS: 
      Hypoxia-inducible factor-1alpha activation positively correlated with RelA activation 
      in clinical gastric cancer samples (P<0.001). The IkappaBalphaM overexpression suppressed 
      tumour growth, microvessel density, and HIF-1alpha activation in xenografted tumours. 
      Cell culture experiments showed that hypoxia-induced HIF-1alpha expression was 
      reduced by NF-kappaB inhibition under hypoxic conditions at the translational level. 
      CONCLUSION: The hypoxia-dependent activation of the NF-kappaB/HIF-1alpha/VEGF pathway 
      contributes, at least in part, to gastric cancer promotion via enhancement of 
      angiogenesis.
FAU - Nam, S Y
AU  - Nam SY
AD  - Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 
      132-703, Korea.
FAU - Ko, Y S
AU  - Ko YS
FAU - Jung, J
AU  - Jung J
FAU - Yoon, J
AU  - Yoon J
FAU - Kim, Y H
AU  - Kim YH
FAU - Choi, Y J
AU  - Choi YJ
FAU - Park, J W
AU  - Park JW
FAU - Chang, M S
AU  - Chang MS
FAU - Kim, W H
AU  - Kim WH
FAU - Lee, B L
AU  - Lee BL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101130
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - I-kappa B Proteins/genetics/metabolism
MH  - Immunoenzyme Techniques
MH  - Luciferases/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/genetics/*metabolism
MH  - Neoplasm Invasiveness
MH  - *Neovascularization, Pathologic
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Stomach Neoplasms/*blood supply/metabolism/*pathology
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC3039796
EDAT- 2010/12/02 06:00
MHDA- 2011/02/16 06:00
PMCR- 2012/01/04
CRDT- 2010/12/02 06:00
PHST- 2010/12/02 06:00 [entrez]
PHST- 2010/12/02 06:00 [pubmed]
PHST- 2011/02/16 06:00 [medline]
PHST- 2012/01/04 00:00 [pmc-release]
AID - 6606020 [pii]
AID - 10.1038/sj.bjc.6606020 [doi]
PST - ppublish
SO  - Br J Cancer. 2011 Jan 4;104(1):166-74. doi: 10.1038/sj.bjc.6606020. Epub 2010 Nov 
      30.