Interferon-gamma and interleukin-6 inhibit proliferation in human melanoma cells by different signalling pathways.
Interferon regulatory factor-1 (IRF-1) is a cell growth inhibitor, induced by cytokines, which transactivates downstream effector genes. The role of IRF-1 in the antiproliferative effect of interleukin-6 (IL-6) was investigated using the A375 human melanoma cell line. IL-6 is a stronger inhibitor of A375 proliferation compared with interferon-gamma (IFNgamma). However, in contrast to IFNgamma, IL-6 triggered lower IRF-1 DNA binding activity and induced barely detectable IRF-1-dependent transactivation activity. Furthermore, although IFNgamma induces only activation of signal transducer and activator of transcription (STAT) 1, IL-6 activates mainly STAT3. These data suggest that IRF-1 plays a minor role in the antiproliferative effect of IL-6, which uses alternative signalling events to induce growth inhibition in A375 melanoma cells.
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Laboratoire de Virologie, Institut Pasteur, Bruxelles, Belgium.
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D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6; D010750:Phosphoproteins; D007371:Interferon-gamma