PMID- 20185296
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20100322
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 46
IP  - 6
DP  - 2010 Apr
TI  - Constitutive HIF-1 activity in malignant melanoma.
PG  - 1159-69
LID - 10.1016/j.ejca.2010.01.031 [doi]
AB  - The hypoxia-inducible factor-1 (HIF-1), which consists of the constitutive 
      HIF-1beta and the oxygen-responsive HIF-1alpha subunit, is the master activator 
      of the cellular transcriptional response to hypoxia coordinating gene expression 
      during reduced oxygen tension. Overexpression of HIF-1 and increased 
      transcriptional activity induced by hypoxia are linked to progression of many 
      tumour types such as head and neck cancer, cervical carcinoma, leukaemia and 
      renal cell carcinoma. In this study, we demonstrate that HIF activity is 
      increased in malignant melanoma cells already under normoxic conditions in 
      contrast to other tumour types. HIF-1alpha and -2alpha knockdown by siRNA 
      transfection revealed that this effect is due to constitutive HIF-1alpha 
      expression. Furthermore, the inhibition or activation of reactive oxygen species 
      (ROS) decreased or activated, respectively, HIF-1 activity and HIF-1alpha protein 
      expression. Interestingly, the inhibition of the NFkappaB pathway also reduced 
      the accumulation of HIF-1alpha assuming a context between ROS and NFkappaB, and 
      suggesting that ROS and NFkappaB activity contribute to HIF-1alpha accumulation. 
      In summary, we identified an increased HIF-1alpha protein expression and activity 
      in melanoma under normoxia mediated by ROS and the NFkappaB pathway.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Kuphal, Silke
AU  - Kuphal S
AD  - University Medical Center Regensburg, D-93053 Regensburg, Germany.
FAU - Winklmeier, Andreas
AU  - Winklmeier A
FAU - Warnecke, Christina
AU  - Warnecke C
FAU - Bosserhoff, Anja-Katrin
AU  - Bosserhoff AK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100223
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/genetics
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Melanoma/genetics/*metabolism
MH  - Mice
MH  - NF-kappa B/genetics/*metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - Skin Neoplasms/genetics/*metabolism
MH  - Transcriptional Activation
EDAT- 2010/02/27 06:00
MHDA- 2010/06/15 06:00
CRDT- 2010/02/27 06:00
PHST- 2009/10/26 00:00 [received]
PHST- 2010/01/15 00:00 [revised]
PHST- 2010/01/21 00:00 [accepted]
PHST- 2010/02/27 06:00 [entrez]
PHST- 2010/02/27 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
AID - S0959-8049(10)00052-3 [pii]
AID - 10.1016/j.ejca.2010.01.031 [doi]
PST - ppublish
SO  - Eur J Cancer. 2010 Apr;46(6):1159-69. doi: 10.1016/j.ejca.2010.01.031. Epub 2010 
      Feb 23.