Linked Life Data

17486380

Source:http://linkedlifedata.com/resource/pubmed/id/17486380

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-6-11
pubmed:abstractText
Overcoming the metabolic restrictions of hypoxia may allow the progression of lower-grade tumors to glioblastoma multiforme. Our findings of up-regulation of HIF-1alpha and its downstream targets VEGF, GLUT-1, and CAIX in higher-grade gliomas support this hypothesis. We compared the gene expression profiles of the U-251 malignant glioma cell line under normoxic and hypoxic conditions to discover future research targets. U-251 cells were grown to 75% confluence and exposed to either normoxic or hypoxic conditions for 24 h. RNA was extracted, amplified, and hybridized to a cDNA microarray chip containing ~8,800 universal cellular genes. A threefold increase in mRNA expression was used as a threshold value for differential expression. Identified genes were divided into cell cycle control, stress response, and "newly connected" genes. Hybridization identified 11 hypoxia-induced genes: 1 involved with cell cycle control (CCNG2), 6 in stress response (IGFBP3, SLC2A3, GSTT2, FOS, DDIT3, AKR1C3), and 2 newly connected genes (Depp, AKAP4). One stress-related gene (AKR1C3) encodes for an enzyme that synthesizes progesterone. Of newly connected genes, the gene decidual protein induced by progesterone (Depp) showed the highest expression (4.2-fold increase). Possible future targeting for "hypoxic" glioma cells includes the targets for the AP-1 transcription factor complex (FOS), as well as blockade of the enzyme AKR1C3 with nonsteroidal anti-inflammatory drugs. Possible functions of the highly expressed gene Depp include tumor vascularization. Future studies will focus on the hypothesis that Depp is up-regulated in an autocrine fashion by the AKR1C3 enzyme in U-251 glioma cells under hypoxic conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0344-5607
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-7; discussion 187
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17486380-Anoxia, pubmed-meshheading:17486380-Brain Neoplasms, pubmed-meshheading:17486380-Cell Hypoxia, pubmed-meshheading:17486380-Cell Line, Tumor, pubmed-meshheading:17486380-Cell Proliferation, pubmed-meshheading:17486380-Cytokines, pubmed-meshheading:17486380-DNA, Complementary, pubmed-meshheading:17486380-DNA, Neoplasm, pubmed-meshheading:17486380-DNA Damage, pubmed-meshheading:17486380-Glioma, pubmed-meshheading:17486380-Glucose Transporter Type 1, pubmed-meshheading:17486380-Humans, pubmed-meshheading:17486380-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:17486380-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:17486380-Nucleic Acid Hybridization, pubmed-meshheading:17486380-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17486380-RNA, Neoplasm, pubmed-meshheading:17486380-Stress, Physiological, pubmed-meshheading:17486380-Up-Regulation, pubmed-meshheading:17486380-Vascular Endothelial Growth Factor A
pubmed:year
2007
pubmed:articleTitle
Identification of hypoxia-induced genes in a malignant glioma cell line (U-251) by cDNA microarray analysis.
pubmed:affiliation
Department of Neurosurgery, University of Utah, Salt Lake City, UT 84132, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't