Linked Life Data

16740701

Source:http://linkedlifedata.com/resource/pubmed/id/16740701

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-6-2
pubmed:abstractText
Tumor hypoxia often directly correlates with aggressive phenotype, metastasis progression, and resistance to chemotherapy. Two transcription factors [hypoxia-inducible factor-1alpha (HIF-1alpha) and HIF-2alpha] are dramatically induced in hypoxic areas and regulate the expression of genes necessary for tumor adaptation to the conditions of low oxygen; however, the relative contribution of these factors is controversial. We used RNA interference-mediated inactivation of HIF-1alpha or HIF-2alpha followed by microarray analysis to identify genes specifically regulated by either HIF-1 or HIF-2 in hypoxia. We found that, in the MCF7 cell line, the vast majority of hypoxia-responsive genes (>80%) were dependent on the presence of HIF-1alpha. However, a small group of genes were preferentially regulated by HIF-2alpha. Promoter analysis for this group of genes revealed that all of them have putative binding sites for ETS family transcription factors, and 10 of 11 HIF-2alpha-dependent genes had at least one potential hypoxia-responsive element (HRE) in proximity to an ETS transcription factor binding site. Knockdown of ELK-1, the most often represented member of ETS family, significantly reduced hypoxic induction of the HIF-2alpha-dependent genes. Physical and functional interaction between ELK-1 and HIF-2alpha were supported by coimmunoprecipitation of these two proteins, luciferase reporter assay using CITED2 promoter, and binding of ELK-1 protein to the promoters of CITED2 and WISP2 genes in proximity to a HRE. These data suggest that the choice of the target genes by HIF-1 or HIF-2 depends on availability and cooperation of HIFs with other factors recognizing their cognate elements in the promoters.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5641-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16740701-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:16740701-Breast Neoplasms, pubmed-meshheading:16740701-Cell Hypoxia, pubmed-meshheading:16740701-Cell Line, Tumor, pubmed-meshheading:16740701-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16740701-Gene Silencing, pubmed-meshheading:16740701-Humans, pubmed-meshheading:16740701-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:16740701-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16740701-Promoter Regions, Genetic, pubmed-meshheading:16740701-Proto-Oncogene Proteins c-ets, pubmed-meshheading:16740701-RNA Interference, pubmed-meshheading:16740701-Transcription Factors, pubmed-meshheading:16740701-Transcriptional Activation, pubmed-meshheading:16740701-ets-Domain Protein Elk-1
pubmed:year
2006
pubmed:articleTitle
Role of ETS transcription factors in the hypoxia-inducible factor-2 target gene selection.
pubmed:affiliation
Laboratory of Biosystems and Cancer, National Cancer Institute, NIH, Bethesda, Maryland, USA. apreliko@mail.nih.gov
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural