Class II transactivator (CIITA) isoform expression and activity in melanoma

• Published in: Melanoma research Vol. 14; no. 6; pp. 453 - 461
• Main Authors: Baton, Fabrice, Deruyffelaere, Carine, Chapin, Muriel, Prod'homme, Thomas, Charron, Dominique, Al-Daccak, Reem, Alcaide-Loridan, Catherine
• Format: Journal Article
• Language: English
• Published: England 01-12-2004
• Subjects: Animals; B-Lymphocytes - metabolism; Cercopithecus aethiops; COS Cells; Cyclin D1 - metabolism; Disease Progression; Eukaryotic Initiation Factor-3; Fibroblasts - metabolism; Gene Expression Regulation, Neoplastic; Genes, MHC Class II - physiology; HLA-DR Antigens - metabolism; Humans; Melanoma - immunology; Melanoma - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Protein Isoforms; Proteins - metabolism; Skin Neoplasms - immunology; Skin Neoplasms - metabolism; Trans-Activators - genetics; Trans-Activators - metabolism; Tumor Cells, Cultured; Tyrosine-tRNA Ligase - metabolism
• ISSN: 0960-8931
• DOI: 10.1097/00008390-200412000-00004

In contrast with melanocytes, melanomas display constitutive expression of HLA-DR (HLA-DR+). This abnormal expression has been associated with tumour progression and metastatic dissemination. We have previously reported that this deregulation of HLA-D genes is due to the abnormal constitutive expression of the lymphocyte-specific isoform of class II transactivator (B-CIITA), in addition to its fibroblast form (F-CIITA), which is usually expressed in major histocompatibility complex (MHC) class II-negative interferon-gamma-induced cell types, such as melanocytes. In this study, we investigated the abnormal expression of B-CIITA in a panel of melanoma cell lines displaying differential HLA-DR expression profiles, and analysed whether such a molecular event can participate in tumour progression. Our results showed that the abnormal expression of B-CIITA did not have any particular effect, in comparison with F-CIITA, on the classical activity of CIITA HLA-D gene regulation. As CIITA has also been shown to regulate genes other than HLA-D, we evaluated the modulation of those encoding cyclin D1, YARS (tyrosyl-tRNA synthetase) and TRIP1 (transforming growth factor (TGF)-beta receptor-interacting protein), proteins involved in cell cycle/apoptosis balance, angiogenesis and resistance to TGF-beta, respectively. In contrast with other cell types, neither B-CIITA nor F-CIITA was able to modulate these genes in melanoma cell lines. Thus, the activity of CIITA, whether lymphocyte-specific or fibroblast-specific, is restricted to HLA-D gene expression in these tumours. Accordingly, our data suggest that CIITA is not involved per se in tumour progression; rather, it is the MHC class II molecules themselves, through tumour antigen presentation and the induction of tumour antigen-specific CD4 lymphocyte anergy, that may participate in immune escape and melanoma progression.