Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator receptor gene expression.
The regulation of urokinase plasminogen activator receptor (uPAR) gene expression by interferon-alpha (IFN-alpha, or Intron A) and interferon-gamma (IFN-gamma) was studied in a HCT116 colon cancer cell line. uPAR mRNA levels were increased in a dose- and time-dependent manner in cells stimulated with IFN-alpha or IFN-gamma. uPAR protein levels reflected IFN-alpha and IFN-gamma induction of uPAR mRNA production. Cycloheximide, a protein synthesis inhibitor, also induced uPAR mRNA accumulation either alone or in combination with IFN-alpha or IFN-gamma, suggesting that the effect on uPAR mRNA levels activated by IFN-alpha or IFN-gamma does not require de novo protein synthesis. Both sodium butyrate and amiloride inhibited the uPAR mRNA levels induced by IFN-alpha or IFN-gamma. These results may provide useful information for the treatment of patients receiving IFN-alpha or IFN-gamma.
Wu
Shanshan
S
Division of Molecular Medicine, John Curtin School of Medical Research, The Australian National University, G.P.O. Box 334, Canberra, ACT 0200, Australia.
Murrell
George A C
GA
Wang
Yao
Y
D000584:Amiloride / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D012978:Sodium Oxybate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018076:DNA, Complementary; D016898:Interferon-alpha; C524898:PLAUR protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D000584:Amiloride; D012978:Sodium Oxybate; D007371:Interferon-gamma; D003513:Cycloheximide