Downregulation of HLA class I expression by c-myc in human melanoma is independent of enhancer A.
High constitutive expression of the c-myc oncogene in human melanoma leads to downregulation of expression of HLA Class I genes. The genes at the HLA-B locus are preferentially affected. To investigate the mechanism of downregulation, the activity of the main HLA Class I enhancer, enhancer A-region I, was compared in a panel of c-myc transfectants with increasing myc expression. Gel retardation experiments demonstrated in all tested cell lines binding of the transcription factors KBF1 and NF-kappa B to the enhancer. However, no correlation between the levels of HLA Class I expression and binding to the enhancer could be established. Strikingly, the cell line with the highest c-myc expression showed more binding of KBF1 and NF-kappa B than the parental cell line. By using CAT reporter plasmids in transient transfection assays we investigated the in vivo function of enhancer A-region I in the c-myc transfectant panel. Again, c-myc expression had no effect at all on the activity of enhancer A. This study shows that HLA Class I expression is regulated by the c-myc oncogene at the level of transcription, but that the main HLA Class I enhancer is not involved in this process.
Peltenburg
L T
LT
Department of Clinical Oncology, University Hospital, Leiden, The Netherlands.
Dee
R
R
Schrier
P I
PI
D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D006801:Humans; D007739:L Cells; D008545:Melanoma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D016271:Proto-Oncogene Proteins c-myc