Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter

In melanoma cell lines, two different patterns of NMC class II expression h ave been described, either in IFN gamma -inducible expression of HLA-DR and HLA-DP, with a faint or null expression of HLA-DQ, resembling that describ ed for melanocytes, or a constitutive expression, i.e., IFN-gamma independe nt, of all three HLA-D isotypes. As this latter phenotype has been associat ed with a more rapid progression of melanoma tumors, we have analyzed in di fferent melanoma cell lines the molecular mechanisms leading to this abnorm al pattern of MHC class II expression. In agreement with the evidence of a coordinate transcription of the HLA-D genes in these cell lines, we have sh own the constitutive expression of CIITA (class II transactivator) transcri pts, CIITA being known as the master switch of MHC class II expression. Une xpectedly, these transcripts initiate from promoter III of the CIITA gene, a promoter that is mainly used constitutively in B lymphocytes. This expres sion was further shown to occur through factor(s) acting on the enhancer lo cated upstream of CIITA promoter III, which was previously described in epi thelioid cells as an IFN-gamma -response sequence. The hypothesis of a gene ral abnormality of the IFN-gamma transduction pathway was dismissed. Consti tutive transcription of CIITA from promoter III having been observed in unr elated melanoma cell lines, we propose the hypothesis that this phenomenon might not be a random event, but could be linked to the neoplasic state of the melanoma cells.