HUMAN UROKINASE RECEPTOR EXPRESSION IS INHIBITED BY AMILORIDE AND INDUCED BY TUMOR-NECROSIS-FACTOR AND PHORBOL ESTER IN COLON-CANCER CELLS

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