Class II transactivator (CIITA) isoform expression and activity in melanoma.
Melanoma Res
; 14(6): 453-61, 2004 Dec.
Article
em En
| MEDLINE
| ID: mdl-15577315
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
/
Proteínas Nucleares
/
Antígenos HLA-DR
/
Regulação Neoplásica da Expressão Gênica
/
Transativadores
/
Melanoma
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Melanoma Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
França