Sensitivity of melanoma cell lines to natural killer cells: a role for oncogene-modulated HLA class I expression?
N-ras and c-myc oncogenes were found to be activated in melanoma. High c-myc expression renders melanoma cell lines sensitive to lysis by natural killer (NK) cells. This effect is mediated by locus-specific downmodulation of HLA-B expression by c-myc. Cell lines with a mutation in the N-ras gene were relatively sensitive to NK cells irrespective of HLA class I expression. These findings indicate that NK cells can kill tumor cells with activated myc or ras oncogenes in various ways, thus providing potential mechanisms to eliminate cancer cells with an activation of these oncogenes.
Schrier
P I
PI
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.
Versteeg
R
R
Peltenburg
L T
LT
Plomp
A C
AC
van 't Veer
L J
LJ
Krüse-Wolters
K M
KM
D015152:Blotting, Northern; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000502:physiology; D015234:HLA-A Antigens / Q000378:metabolism; D015235:HLA-B Antigens / Q000378:metabolism; D015236:HLA-C Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D009857:Oncogenes / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D001613:beta 2-Microglobulin