PMID- 12458176
OWN - NLM
STAT- MEDLINE
DCOM- 20030711
LR  - 20191106
IS  - 1532-0456 (Print)
IS  - 1532-0456 (Linking)
VI  - 133
IP  - 4
DP  - 2002 Dec
TI  - Characterization of HIF-1 alpha overexpressing HeLa cells and implications for 
      gene therapy.
PG  - 475-81
AB  - Upon exposing mammalian tissues to hypoxia, expression of a number of 
      physiologically important genes such as erythropoietin and vascular endothelial 
      growth factor (VEGF) increases. The key regulator for this oxygen-dependent gene 
      expression is the hypoxia-inducible factor-1 (HIF-1), a heterodimeric 
      transcription factor consisting of an alpha and a beta subunit. Both HIF-1 
      subunits are widely expressed in the cells and tissue of vertebrates, flies, 
      fishes, worms and probably most other species. The beta subunit (also termed 
      ARNT, aryl hydrocarbon receptor nuclear translocator) is abundantly expressed in 
      an oxygen-independent manner. On the other hand, HIF-1alpha cannot be detected 
      above a critical partial pressure of oxygen when it is subjected to rapid 
      ubiquitinylation and proteasomal degradation. Hypoxic exposure leads to 
      stabilization of HIF-1alpha protein and subsequent activation of HIF-1-dependent 
      target genes. HIF-1 is not only a master regulator of oxygen homeostasis, it also 
      appears to play a key role in tumor development as well as cardiovascular and 
      ischemic diseases. Genetic modulation of HIF-1alpha activity in vivo may 
      therefore represent a novel therapeutic approach to these disorders. In this 
      overview, we report on the generation of HIF-1alpha overexpressing HeLa cell 
      lines and demonstrate the feasibility of normoxic HIF-1 gene transfer in vitro 
      and in vivo thereby identifying the limiting steps for full activation of HIF-1.
FAU - Hofer, Thomas
AU  - Hofer T
AD  - Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, 
      Zurich, Switzerland.
FAU - Desbaillets, Isabelle
AU  - Desbaillets I
FAU - Hopfl, Gisele
AU  - Hopfl G
FAU - Wenger, Roland H
AU  - Wenger RH
FAU - Gassmann, Max
AU  - Gassmann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Comp Biochem Physiol C Toxicol Pharmacol
JT  - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
JID - 100959500
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lymphokines)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - Animals
MH  - Drug Delivery Systems/*methods
MH  - Endothelial Growth Factors/biosynthesis/genetics
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Genetic Therapy/*methods
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Intercellular Signaling Peptides and Proteins/biosynthesis/genetics
MH  - Lymphokines/biosynthesis/genetics
MH  - Transcription Factors/*biosynthesis/*genetics
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
RF  - 42
EDAT- 2002/11/30 04:00
MHDA- 2003/07/12 05:00
CRDT- 2002/11/30 04:00
PHST- 2002/11/30 04:00 [pubmed]
PHST- 2003/07/12 05:00 [medline]
PHST- 2002/11/30 04:00 [entrez]
AID - S1532045602001175 [pii]
AID - 10.1016/s1532-0456(02)00117-5 [doi]
PST - ppublish
SO  - Comp Biochem Physiol C Toxicol Pharmacol. 2002 Dec;133(4):475-81. doi: 
      10.1016/s1532-0456(02)00117-5.