PMID- 15833847
OWN - NLM
STAT- MEDLINE
DCOM- 20050603
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 8
DP  - 2005 Apr 15
TI  - Anoxia is necessary for tumor cell toxicity caused by a low-oxygen environment.
PG  - 3171-8
AB  - Cells exposed to oxygen deprivation in vitro have been shown to reduce 
      proliferation and/or engage in programmed cell death. There is considerable 
      controversy in the literature as to the role of hypoxia-inducible factor-1 
      (HIF-1) and HIF-1 target genes in initiating these responses. We therefore 
      examined the oxygen dependence and the role of the hypoxia-responsive 
      transcription factor HIF-1 in making the cellular death decision. Oxygen 
      concentrations as low as 0.5% did not alter the growth of HIF-1-proficient or 
      HIF-1-deficient murine fibroblasts, or human tumor cells, despite the appropriate 
      induction of HIF-1 target genes. Severe hypoxia (<0.01% oxygen) did induced 
      apoptosis, resulting in decreased colony formation, chromatin condensation, DNA 
      fragmentation, and caspase activation but also independent of HIF1alpha status. 
      Transcriptional induction of HIF-1-dependent genes putatively involved in cell 
      death like BNip3 and BNip3L was therefore disassociated from hypoxia-dependent 
      toxicity. Likewise, forced overexpression of a nondegradable form of HIF-1alpha 
      in several human tumor cell lines was not sufficient to induce apoptosis under 
      normoxic conditions. Taken together, these findings indicate that additional 
      molecular events are triggered by anoxia in a HIF-1-independent manner, and these 
      changes are necessary for cell death observed in low-oxygen environments.
FAU - Papandreou, Ioanna
AU  - Papandreou I
AD  - Department of Radiation Oncology, Division of Radiation and Cancer Biology, 
      Stanford University School of Medicine, Stanford, California, USA.
FAU - Krishna, Chaya
AU  - Krishna C
FAU - Kaper, Fiona
AU  - Kaper F
FAU - Cai, Deli
AU  - Cai D
FAU - Giaccia, Amato J
AU  - Giaccia AJ
FAU - Denko, Nicholas C
AU  - Denko NC
LA  - eng
GR  - CA67166/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (BNIP3 protein, human)
RN  - 0 (BNIP3L protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cell Hypoxia/*physiology
MH  - DNA-Binding Proteins/biosynthesis/deficiency/genetics/*physiology
MH  - Fibroblasts/cytology/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Membrane Proteins/biosynthesis/genetics/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Neoplasms/genetics/metabolism/*pathology
MH  - Nuclear Proteins/biosynthesis/deficiency/genetics/*physiology
MH  - Oxygen/*metabolism
MH  - Proto-Oncogene Proteins/biosynthesis/genetics/physiology
MH  - Transcription Factors/biosynthesis/deficiency/genetics/*physiology
MH  - Tumor Suppressor Proteins/biosynthesis/genetics/physiology
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 - 65/8/3171 [pii]
AID - 10.1158/0008-5472.CAN-04-3395 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Apr 15;65(8):3171-8. doi: 10.1158/0008-5472.CAN-04-3395.