High expression of the c-myc oncogene renders melanoma cells prone to lysis by natural killer cells.
NK cells kill a wide variety of tumor cells, but usually leave normal cells intact. It was earlier reported that low class I HLA expression can be one of the factors that render target cells relatively susceptible to NK lysis. In this contribution, we show that in human melanomas the class I HLA expression is down-modulated by high expression of transfected c-myc oncogenes. The extent of down-modulation depended on the level of c-myc expression in a dose-dependent way. Taken together, these data suggested to us that one of the results of high c-myc expression could be the induction of a NK susceptible phenotype in melanoma cells. Therefore, we analyzed the effect of c-myc on NK susceptibility. We have found that high expression of transfected c-myc genes indeed converts the melanoma cell lines from poor into good targets for NK cells. IFN-gamma was used to restore the class I HLA expression of the c-myc transfectants, and the resulting cells showed a decreased NK susceptibility. These results suggest the possibility that the c-myc-induced NK susceptibility is mediated by the reduction of class I HLA expression.
Versteeg
R
R
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.
Peltenburg
L T
LT
Plomp
A C
AC
Schrier
P I
PI
D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000235:genetics* / Q000276:immunology; D009857:Oncogenes / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma