title: c-Myc and EBV-LMP1: two opposing regulators of the HLA class I antigen presentation machinery in epithelial cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pathology, Department of Nephropathology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany. Silke.Tudor@uk-erlangen.de
authors.forename: C S
authors.initials: CS
authors.lastname: Tudor
authors.forename: C W
authors.initials: CW
authors.lastname: Dawson
authors.forename: J
authors.initials: J
authors.lastname: Eckhardt
authors.forename: G
authors.initials: G
authors.lastname: Niedobitek
authors.forename: A C
authors.initials: AC
authors.lastname: Büttner
authors.forename: B
authors.initials: B
authors.lastname: Seliger
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: M
authors.initials: M
authors.lastname: Buettner
mesh_terms: D017951:Antigen Presentation / Q000235:genetics*; D002277:Carcinoma; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014763:Viral Matrix Proteins