Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-4-24
pubmed:abstractText
Both hypoxia and overexpression of the urokinase plasminogen activator receptor (uPAR) are associated with a poor clinical outcome in human cancers. Hypoxia has been shown to induce uPAR expression in breast cancer cells and to increase their invasion through Matrigel, a phenomenon which can be blocked using an anti-uPAR antibody. We examined expression of uPAR mRNA in MCF7 human breast carcinoma cells under hypoxia and found that an increase in the level of the message could be detected at 1% oxygen but was most marked at 0.2 or 0.05% oxygen with an induction of 9- to 20-fold over baseline. To determine whether changes in RNA stability contributed to this dramatic increase, we used actinomycin D to inhibit transcription and found that the half-life of the message was much longer under hypoxic conditions (approximately 10 h) than during reoxygenation (approximately 2 h). Transient transfections using a luciferase reporter construct containing 2 kbp of the mouse uPAR promoter showed that promoter activity increased up to 5-fold after exposure to 0.2% oxygen. Thus, hypoxic induction of the uPAR message in MCF7 cells is due to both mRNA stabilization and increased transcriptional activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
255
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
250-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Both increased stability and transcription contribute to the induction of the urokinase plasminogen activator receptor (uPAR) message by hypoxia.
pubmed:affiliation
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA. maity@mail.med.upenn.edu
pubmed:publicationType
Journal Article