PMID- 10933058
OWN - NLM
STAT- MEDLINE
DCOM- 20000906
LR  - 20190607
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Electronic)
IS  - 1476-5586 (Linking)
VI  - 1
IP  - 5
DP  - 1999 Nov
TI  - Killing of brain tumor cells by hypoxia-responsive element mediated expression of 
      BAX.
PG  - 431-7
AB  - The presence of radioresistant hypoxic cells in human brain tumors limits the 
      overall effectiveness of conventional fractionated radiation therapy. 
      Tumor-specific therapies that target hypoxic cells are clearly needed. We have 
      investigated the expression of suicide genes under hypoxia by a 
      hypoxia-responsive element (HRE), which can be activated through 
      hypoxia-inducible factor-1 (HIF-1). We transfected plasmids containing multiple 
      copies of HRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested 
      their ability to induce LacZ gene expression under anoxia. Gene expression under 
      anoxia versus oxia was increased about 12-fold for U-87 MG cells and about 
      fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased 
      LacZ gene expression in U-87 MG cells was induced by the plasmid that contained 
      three HREs, but not by the plasmid with two HREs. Lastly, when we placed a 
      suicide gene BAX under the control of HREs, cells transfected with the BAX 
      plasmids were preferentially killed through apoptosis under anoxia. Our studies 
      demonstrate that HRE-regulated gene expression is active in brain tumor cells, 
      and that the amount of increased gene expression obtained is dependent on the 
      cell line, the HRE copy number, and the degree of hypoxia.
FAU - Ruan, H
AU  - Ruan H
AD  - Brain Tumor Research Center of the Department of Neurological Surgery, University 
      of California, San Francisco 94143-0520, USA.
FAU - Wang, J
AU  - Wang J
FAU - Hu, L
AU  - Hu L
FAU - Lin, C S
AU  - Lin CS
FAU - Lamborn, K R
AU  - Lamborn KR
FAU - Deen, D F
AU  - Deen DF
LA  - eng
GR  - T32 CA009215/CA/NCI NIH HHS/United States
GR  - CA-09215/CA/NCI NIH HHS/United States
GR  - CA-13525/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (BAX protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Transcription Factors)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Brain Neoplasms/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Glioma/*genetics
MH  - Humans
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - In Situ Nick-End Labeling
MH  - Lac Operon/genetics
MH  - Luciferases/metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Oxygen/metabolism
MH  - Plasmids
MH  - Proto-Oncogene Proteins/*biosynthesis
MH  - *Proto-Oncogene Proteins c-bcl-2
MH  - *Transcription Factors
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - bcl-2-Associated X Protein
MH  - beta-Galactosidase/metabolism
PMC - PMC1508106
EDAT- 2000/08/10 11:00
MHDA- 2000/09/09 11:01
PMCR- 1999/11/01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2000/09/09 11:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
PHST- 1999/11/01 00:00 [pmc-release]
AID - 0059a [pii]
AID - 10.1038/sj.neo.7900059 [doi]
PST - ppublish
SO  - Neoplasia. 1999 Nov;1(5):431-7. doi: 10.1038/sj.neo.7900059.