Suppression of basal, PMA- and IFN-alpha-, but not IFN-gamma-induced expression of HLA class I in v-myc-transformed U-937 monoblasts.
Recent studies have suggested that certain oncogenes, in particular members of the myc family, may be involved in the down-regulation of HLA class-I antigen expression observed in many types of tumor. We report that constitutive expression of an OK10 v-myc gene in human monoblastic U-937 cells results in a reduced expression of HLA class-I cell-surface expression and decreased levels of HLA class-I protein and mRNA. All class-I alleles, with the possible exception of HLA A3, were affected, as shown by one-dimensional isoelectric focusing (ID-IEF). Basal expression of the beta 2m chain was also reduced, although to a lesser extent. In addition, we show that the PMA-, and at least partially the IFN-alpha-induced increase in HLA class-I antigen expression, was inhibited in U-937-myc cells both at the protein and the mRNA level. In contrast, the response to IFN-gamma was normal. Another important difference in the response to IFN-gamma and alpha was that, while IFN-gamma abrogated the v-myc block of PMA-induced differentiation of U-937 cells, as previously reported, IFN-alpha did not. Our data show that v-myc negatively affects the regulation of both basal and inducible HLA class-I antigen expression.
Department of Pathology, University of Uppsala, University Hospital, Sweden.
L G
LG
Larsson
F
F
Oberg
P
P
Stöckbauer
M G
MG
Masucci
K
K
Nilsson
D000483:Alleles; D015703:Antigens, CD / Q000378:metabolism; D018845:CD11 Antigens; D002455:Cell Division; D002472:Cell Transformation, Viral / Q000235:genetics*; D005786:Gene Expression Regulation; D016259:Genes, myc; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018845:CD11 Antigens; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D012333:RNA, Messenger; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate