DOWN-REGULATION 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-kappaB 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-kappaB 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.