• 1 December 1986
    • journal article
    • research article
    • Vol. 46  (12) , 6211-6216
Abstract
We studied the mechanisms of resistance to inferferon (IFN) in two human melanoma cell lines, SK-MEL-28/.beta. cells resistant to human recombinant .beta.-interferon (ReIFN-.beta.) and SK-MEL-28/.gamma. cells resistant to human rcombinant .gamma.-interferon (ReIFN-.gamma.). SK-MEL-28/.beta. cells were resistant to both ReIFN-.beta. and IFN-.alpha. but not ReIFN-.gamma. or natural .gamma.-inteferon (IFN-.gamma.), and SK-MEL-28/.gamma. cells were resistant to both ReIFN-.gamma. and IFN-.gamma., but not ReIFN-.beta. or IFN-.alpha.. SK-MEL-28/s cells, sensitive to both ReIFN-.beta. and ReIFN-.gamma., had receptors for ReIFN-.beta. and ReIFN-.gamma.. Furthermore ReIFN-.beta. and IFN-.alpha. shared the common receptors as judged by competition assays, while the receptors for ReIFN-.gamma. were independent in SK-MEL-28/s cells. The Kd values of binding of both IFNs to SK-MEL-28/.beta. or SK-MEL-28/.gamma. cells were essentially equivalent to those to SK-MEL-28/s cells. Both labeled IFNs were internalized rapidly into all cell lines at 37.degree. C. No significant difference in internalization was found between IFN-sensitive and -resistant cells. Each cell line expressed HLA-AB and Mr 97,000 protein antigens, the expressions of which were enhanced by ReIFN-.beta. and ReIFN-.gamma.. Partial resistance to the enhancement of both antigens by both IFNs was seen in the resistant cells. Finally ReIFN-.gamma., but not ReIFN-.beta., induced a Mr 56,000 protein in SK-MEL-28/s cells. This effect of ReIFN-.gamma. was also detected in SK-MEL-28/.beta. cells, but not SK-MEL-28/.gamma. cells. These results provide some information concerning the nature of IFN-resistant cells. The receptors had no significant correlation with the resistance, while the expression of HLA-AB or Mr 97,000 protein antigens or the induction of proteins had some correlation with the resistance.

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