INTERFERON-GAMMA AND INTERLEUKIN-6 INHIBIT PROLIFERATION IN HUMAN-MELANOMA CELLS BY DIFFERENT SIGNALING PATHWAYS

Interferon regulatory factor-1 (IRF-1) is a cell growth inhibitor, ind uced 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 s tronger inhibitor of A375 proliferation compared with interferon-gamma (IFN gamma). However, in contrast to IFN gamma, IL-6 triggered lower IRF-1 DNA binding activity and induced barely detectable IRF-1-depende nt transactivation activity. Furthermore, although IFN gamma induces o nly activation of signal transducer and activator of transcription (ST AT) 1, IL-6 activates mainly STAT3. These data suggest that IRF-1 play s a minor role in the antiproliferative effect of IL-6, which uses alt ernative signalling events to induce growth inhibition in A375 melanom a cells. (C) 1998 Rapid Science Ltd.