c-myc-induced natural killer cell sensitivity of human melanoma cells is reversed by HLA-B27 transfection.
In human melanoma, activation of the c-myc oncogene results in locus-specific down-modulation of the HLA-B antigen expression. Moreover, overexpression of c-myc induces an increase of natural killer (NK) sensitivity of the tumor cells. To show that this effect on susceptibility to NK cells is mediated by the down-modulation of the HLA-B expression rather than by the activation of the oncogene, we supertransfected a c-myc transfectant with the gene encoding the HLA-B27 protein. The resulting supertransfectants with HLA-B27 surface expression were all less sensitive to NK cells than their parental cell line and showed a level of resistance equal to the original melanoma cell line with low c-myc expression. This indicates that the induction of NK sensitivity by c-myc activation in human melanoma cells is mediated through down-modulation of the HLA-B expression. These data also imply differential effects of HLA-A and HLA-B molecules on lysis by NK cells, because the level of NK susceptibility can apparently be defined by the level of HLA-B, irrespective of a substantial level of HLA-A expression present in the tumor cells.
Peltenburg
L T
LT
University Hospital, Department of Clinical Oncology, Leiden, The Netherlands.
Steegenga
W T
WT
Krüse
K M
KM
Schrier
P I
PI
D015870:Gene Expression; D016259:Genes, myc; D015234:HLA-A Antigens / Q000032:analysis; D015796:HLA-B27 Antigen / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015234:HLA-A Antigens; D015796:HLA-B27 Antigen