The JAK/STAT pathway is not sufficient to sustain the antiproliferative response in an interferon-resistant human melanoma cell line

Melanoma Research
David P JacksonPoulam M Patel

Abstract

The mechanism of resistance of malignant melanoma to treatment with interferon-alpha is unknown, and currently there is no reliable method of predicting response. Signalling via the JAK/STAT pathway is known to mediate many interferon-regulated events and has been implicated in mediating the antiproliferative response. The objective of this study was to determine whether defects in JAK/STAT signalling may be responsible for interferon resistance. The in vitro response to interferon was determined in a panel of established melanoma cell lines, and the components and functioning of the JAK/STAT pathway were examined in sensitive and resistant cell lines. Two melanoma cell lines, characterized as sensitive (MM418) and resistant (MeWo) to the antiproliferative effect of interferon, were both shown by Western blotting to possess all the protein components of the JAK/STAT pathway, and were shown to be capable of producing functional transcription factors using an electrophoretic mobility shift assay and a ribonuclease protection assay of known interferon-induced genes. In addition, both cell lines had intact antiviral and HLA upregulation responses. These data suggest that there is no defect in the JAK/STAT pathway per se in the MeWo...Continue Reading

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Apr 28, 2009·Cancer Immunology, Immunotherapy : CII·Gregory B LesinskiWilliam E Carson
Sep 25, 2004·Journal of Cellular Physiology·Michele CaragliaAlberto Abbruzzese
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