Over-expression of C-myc increases the sensitivity of Epstein-Barr virus immortalized lymphoblastoid cells to non-MHC-restricted cytotoxicity.
Epstein-Barr virus (EBV)-carrying Burkitt lymphoma (BL) lines which maintain the phenotypic characteristics of the in vivo tumor cells are more sensitive to natural (NK), interferon-activated (IAK) and IL-2-activated (LAK) cytotoxicity than EBV-immortalized lymphoblastoid cell lines (LCL) of normal B-cell origin. All BL cells carry chromosomal translocations which lead to deregulated expression of the c-myc oncogene. LCLs transfected with constitutively active c-myc alleles display changes in growth properties and surface phenotype. In this study, we have examined the effect of c-myc deregulation on the sensitivity of LCLs to NK, IAK and LAK effectors. C-myc-transfected LCLs showed an increased sensitivity to lysis which correlated with the level of c-myc expression. Expression of HLA class I and sensitivity to allospecific and EBV-specific cytotoxic T-lymphocytes (CTL) remained unchanged. Transfection of a constitutively active v-H-ras gene, which also induces changes in growth properties and cell-surface phenotype, did not alter the sensitivity of LCLs to NK or LAK cytotoxicity.
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
L
L
Cuomo
Q J
QJ
Zhang
L
L
Lombardi
S
S
Torsteinsdottir
G
G
Klein
R
R
Dalla-Favera
M G
MG
Masucci
D002472:Cell Transformation, Viral / Q000235:genetics*; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D011994:Recombinant Proteins