Human urokinase receptor expression is inhibited by amiloride and induced by tumor necrosis factor and phorbol ester in colon cancer cells

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Abstract
The modulation of urokinase plasminogen activator receptor (uPAR) gene expression by tumor necrosis factor alpha (TNFα), phorbol ester (PMA) and amiloride was studied in three colon cancer cell lines. uPAR mRNA and protein were induced by TNFα and by PMA but were inhibited by amiloride at concentrations of 0.1 to 1 mM in the presence or absence of TNFα and PMA. Nuclear run‐on transcription assay indicated that the effects of amiloride and TNFα were mediated at least in part at the transcriptional level, whereas PMA may act in part via a post‐transcriptional mechanism. These results suggested that uPAR gene expression is modulated by multiple signal transduction pathways.