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Unité Institut National de la Santé et de la Recherche Médicale, Unité 396, Centre de Recherches Biomédicales des Cordeliers, Paris, France;
Unité Institut National de la Santé et de la Recherche Médicale, Unité 429, Hôpital Necker, Paris, France;
Department of Basic Sciences, Mercer University Medical School, Macon, GA 31207; and
Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599
In melanoma cell lines, two different patterns of MHC class II
expression have been described, either an IFN 
-inducible expression
of HLA-DR and HLA-DP, with a faint or null expression of HLA-DQ,
resembling that described for melanocytes, or a constitutive
expression, i.e., IFN- independent, of all three HLA-D isotypes. As
this latter phenotype has been associated with a more rapid progression
of melanoma tumors, we have analyzed in different melanoma cell lines
the molecular mechanisms leading to this abnormal 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 shown the constitutive expression of CIITA (class
II transactivator) transcripts, CIITA being known as the master switch
of MHC class II expression. Unexpectedly, these transcripts initiate
from promoter III of the CIITA gene, a promoter that is
mainly used constitutively in B lymphocytes. This expression was
further shown to occur through factor(s) acting on the enhancer located
upstream of CIITA promoter III, which was previously
described in epithelioid cells as an IFN--response sequence. The
hypothesis of a general abnormality of the IFN- transduction pathway
was dismissed. Constitutive transcription of CIITA from
promoter III having been observed in unrelated 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.
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