PMID- 15833863
OWN - NLM
STAT- MEDLINE
DCOM- 20050603
LR  - 20181201
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 8
DP  - 2005 Apr 15
TI  - Differential gene up-regulation by hypoxia-inducible factor-1alpha and 
      hypoxia-inducible factor-2alpha in HEK293T cells.
PG  - 3299-306
AB  - Cells exposed to hypoxia respond by increasing the level of hypoxia-inducible 
      factor-1 (HIF-1). This factor then activates a number of genes by binding to 
      hypoxia response elements in their promoter regions. A second hypoxia-responsive 
      factor, HIF-2, can activate many of the same genes as HIF-1. Overexpression of 
      HIFs accompanies the pathogenesis of many tumors. It is unclear, however, as to 
      the respective role of these factors in responsiveness to hypoxia and other 
      stresses. To address this issue, we used microarray technology to study the genes 
      activated in HEK293T cells by hypoxia or transfection with the alpha chain of 
      HIF-1 (or mutant HIF-1 resistant to degradation) or HIF-2. Fifty-six genes were 
      found to be up-regulated at least 3-fold by either hypoxia or transfection. Of 
      these, 21 were elevated both by transfection with HIF-1alpha and with HIF-2alpha, 
      and 14 were preferentially activated by HIF-1alpha including several involved in 
      glycolysis. Ten genes were preferentially activated by HIF-2alpha, including two 
      (CACNA1A and PTPRZ1) implicated in neurologic diseases. Interestingly, most 
      HIF-2alpha-responsive genes were not substantially activated by hypoxia. An 
      additional 10 genes were up-regulated by hypoxia but minimally activated by 
      HIF-1alpha or HIF-2alpha transfection. Ten of the genes were studied by 
      quantitative real-time PCR and/or by Northern blot and the results paralleled 
      those found with microarray technology. Although confirmation in other systems 
      will be necessary, these results indicate that whereas some genes are robustly 
      activated by both HIF-1 and HIF-2, others can be preferentially activated by one 
      or the other factor.
FAU - Wang, Victoria
AU  - Wang V
AD  - HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer 
      Institute, NIH, Bethesda, MD 20892, USA.
FAU - Davis, David A
AU  - Davis DA
FAU - Haque, Muzammel
AU  - Haque M
FAU - Huang, L Eric
AU  - Huang LE
FAU - Yarchoan, Robert
AU  - Yarchoan R
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
SB  - IM
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Blotting, Northern
MH  - Cell Hypoxia/genetics
MH  - Cell Line
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Kidney/cytology/metabolism/physiology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Trans-Activators/biosynthesis/*genetics
MH  - Transcription Factors/biosynthesis/*genetics
MH  - Transfection
MH  - Up-Regulation/*genetics
EDAT- 2005/04/19 09:00
MHDA- 2005/06/04 09:00
CRDT- 2005/04/19 09:00
PHST- 2005/04/19 09:00 [pubmed]
PHST- 2005/06/04 09:00 [medline]
PHST- 2005/04/19 09:00 [entrez]
AID - 65/8/3299 [pii]
AID - 10.1158/0008-5472.CAN-04-4130 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Apr 15;65(8):3299-306. doi: 10.1158/0008-5472.CAN-04-4130.