Abnormal expression of Major Histocompatibility Complex class II (MHC II) molecules in melanoma

Melanoma, a solid tumour that arise from pigment producing melanocytes, is the most aggressive and lethal type form of cutaneous cancer in Caucasian light skin population. The melanoma cells often display a constitutive expression of the Major Histocompatibility Complex (MHC) class II molecules which is usually restricted to professional antigen-presenting cells (APCs). Paradoxically, the constitutive MHC class II expression by these tumours is associated with a better progression of primary melanoma and a higher metastatic dissemination rather than with tumour regression. We have analysed the molecular mechanisms leading to the abnormal constitutive expression of MHC class II molecules in different melanoma cell lines and we have observed the constitutive expression of the two major isoforms of the class II transactivator (CIITA) protein, the master switch of MHC class II gene, that are differentially expressed in B lymphocytes and fibroblast cell lines. Our data therefore demonstrate that the respective ratio of CIITA isoforms depends on the cell type examined and we present evidence for a modulation of this ratio in a MHC class II constitutive expressing melanoma cell line.