Resistance to Interferons in Melanoma Cells Does Not Correlate with the Expression or Activation of Signal Transducer and Activator of Transcription 1 (Stat1)
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Defects in expression or activation signal transducer and activator of transcription-1 (Stat1) in response to interferon-α2 (IFN-α2) have been implicated as a mechanism for IFN resistance in melanoma cells. To further determine the significance of this observation, 17 melanoma cell lines sensitive or resistant to the antiproliferative effects of IFN-α2 and IFN-β, as well as 30 melanoma patient samples, were analyzed for Stat1 levels by either Western blot analysis or immunohistochemistry. Although the expression level varied between samples, all the cell lines except one and all melanoma biopsy specimens expressed Stat1. IFN-stimulated levels of Stat1 and Stat2, which constitute the transcriptional activation complexes, such as, gamma activated factor (GAF) and IFN-stimulated gene factor 3 (ISGF3), for IFN-stimulated gene (ISG) induction were assessed in melanoma cell lines. Both IFN-α2 and INF-β induced equivalent amounts of Stat1 and Stat2 proteins in cell lines, although compared with IFN-α2, IFN-β had greater antiproliferative effects. No significant differences were observed in tyrosine or serine phosphorylation of Stat1 or the formation of GAF or ISGF3 complexes following IFN-α2 or IFN-β treatment of IFN-resistant or IFN-sensitive cell lines. Comparable induction of two ISGs, ISG54 and IFN regulatory factor-1 (IRF-1), was observed in both sensitive WM9 and resistant A375 cells. Therefore, we report that defects in expression or activation of Stat1 or Stat2 were infrequent in melanoma cell lines and tumor samples and did not correlate with IFN resistance. Cellular resistance to IFNs likely results from defective quantitative or qualitative expression of specific ISGs.
Leaman, D. W.,
Jacobs, B. S.,
Tuthill, R. J.,
Stark, G. R.,
& Borden, E. C.
(2002). Resistance to Interferons in Melanoma Cells Does Not Correlate with the Expression or Activation of Signal Transducer and Activator of Transcription 1 (Stat1). Journal of Interferon and Cytokine Research, 22 (5), 63-613.