Interferon-gamma, but not interferon-alpha, induces SOCS 3 expression in human melanoma cell lines.
The signal transducers and transcription activators (STATs) and their endogenous inhibitors of the suppressors of cytokine signalling (SOCS) family are major proteins harmonizing the transmission of external signals from the surface membrane to target genes in the nucleus. To correlate the induction of SOCS 3 by interferons (IFNs) on messenger RNA and protein levels with STAT 1 phosphorylation in human malignant melanoma cell lines, we used a unique collection of 18 established malignant melanoma cell lines and six human non-malignant normal cells (two melanocytes, two skin keratinocytes and two fibroblasts). IFN-gamma induced SOCS 3 in 83% of melanoma cell lines, whereas IFN-alpha stimulated SOCS 3 expression in only 11% of cases. Similarly, melanocytes showed strong induction of SOCS 3 by IFN-gamma and, to a lesser extent, by IFN-alpha. In most cases, SOCS 3 expression was paralleled by STAT 1 phosphorylation at tyrosine residues (Y701). In several lines, however, SOCS 3 was not induced despite STAT 1 phosphorylation and, in a few lines, SOCS 3 induction occurred without detectable STAT 1 phosphorylation, indicating that STAT 1 might not be an exclusive inducer of SOCS 3. Similarly, non-malignant cells displayed STAT 1 activation and high levels of SOCS 3 expression after IFN-gamma (but not IFN-alpha) treatment. In conclusion, in contrast to IFN-alpha, IFN-gamma appeared to induce SOCS 3 apparently at the transcription level and exhibited higher cytotoxic effects regardless of the cell origin.
Kovarik
Ales
A
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Fojtova
Miloslava
M
Boudny
Vladimir
V
Adamkova
Lenka
L
Lauerova
Ludmila
L
Kovarik
Jan
J
D015152:Blotting, Northern; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics
D007370:Interferon Type I; D012333:RNA, Messenger; D011994:Recombinant Proteins; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma