Abstract
The effects of butyrate on the modulation of urokinase plasminogen activator (uPA) and its receptor (uPAR) mRNAs were studied. While both mRNA levels were increased after stimulation by tumor necrosis factor alpha (TNF alpha), phorbol ester (PMA) and cycloheximide, they were inhibited by butyrate at 2.5 to 25 mM. Nuclear run-on transcription assays indicated that uPA mRNA was modulated by butyrate at the transcriptional level but the uPAR gene was regulated at both transcriptional and post-transcriptional levels in the presence or absence of TNF alpha. In the presence of PMA, however, butyrate acts at the post-transcriptional level on both genes.
MeSH terms
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Butyrates / pharmacology*
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Butyric Acid
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Cycloheximide / pharmacology
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Gene Expression / drug effects
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Humans
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Phorbol Esters / pharmacology
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RNA, Messenger / biosynthesis*
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Receptors, Cell Surface / biosynthesis*
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Receptors, Cell Surface / genetics
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Receptors, Urokinase Plasminogen Activator
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Transcription, Genetic* / drug effects
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology
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Urokinase-Type Plasminogen Activator / biosynthesis*
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Urokinase-Type Plasminogen Activator / genetics
Substances
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Butyrates
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PLAUR protein, human
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Phorbol Esters
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Urokinase Plasminogen Activator
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Tumor Necrosis Factor-alpha
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Butyric Acid
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Cycloheximide
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Urokinase-Type Plasminogen Activator