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Br J Cancer ; 106(12): 1980-8, 2012 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-22588558

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) up-regulates the human leukocyte antigen (HLA) class I antigen presentation machinery (APM). This appears counterintuitive with immune evasion in EBV-associated tumours like nasopharyngeal carcinoma (NPC). METHODS: Latent membrane protein 1-transfected epithelial cell lines were used as a model system to study the impact of LMP1 and c-Myc on HLA class I components. The expression of components of the HLA class I APM, c-Myc and Ki-67 was analysed in LMP1+ and LMP1- NPC by immunohistochemistry. RESULTS: In epithelial cells, LMP1 up-regulated HLA class I APM. This effect could be counteracted by c-Myc, which itself was up-regulated by LMP1 apparently through IL6 induction and Jak3/STAT3 activation. Studies of NPC biopsies revealed down-regulation of HLA class I APM expression. No difference was observed between LMP1+ and LMP1- NPC. However, expression of Ki-67 and c-Myc were up-regulated in LMP1+ tumours. CONCLUSION: These findings raise the possibility that c-Myc activation in NPC might antagonise the effect of LMP1 on HLA class I expression thus contributing to immune escape of tumour cells.


Assuntos
Apresentação de Antígeno/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas da Matriz Viral/metabolismo , Carcinoma , Linhagem Celular Tumoral , Células Epiteliais/imunologia , Humanos , Interleucina-6/metabolismo , Carcinoma Nasofaríngeo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Regulação para Cima
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