Different levels of control prevent interferon-γ-inducible HLA-class II expression in human neuroblastoma cells

Michela Croce, Alessandro De Ambrosis, Maria V. Corrias, Vito Pistoia, Marzia Occhino, Raffaella Meazza, Julien Giron-Michel, Bruno Azzarone, Roberto S. Accolla, Silvano Ferrini

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The HLA class II expression is controlled by the transcriptional activator CIITA. The transcription of CIITA is controlled by different promoters, among which promoter-IV is inducible by IFN-γ. We analysed the regulation of HLA class II molecules by IFN-γ in a large series of human neuroblastoma cell lines. No induction of surface or intracellular HLA class II molecules and of specific mRNA was observed, in all neuroblastomas, with the exception of a nonprototypic cell line, ACN. In a large subset of neuroblastomas IFN-γ induced expression of CIITA mRNA, derived from promoter-IV, which was not methylated. In contrast, in another subset of neuroblastomas, CIITA was not inducible by IFN-γ and CIITA promoter-IV was either completely or partially methylated. Interestingly, the use of DNA demethylating agents restored CIITA gene transcriptional activation by IFN-γ, but not HLA class II expression. The defect of HLA class II was not related to alterations in RFX or NF-Y transcription factors, as suggested by EMSA or RFX gene transfection experiments. In addition, the transfection of a functional CIITA cDNA failed to induce HLA class II expression in typical neuroblastoma cells. Confocal microscopy and Western blot analysis suggested a defective nuclear translocation and/or reduced protein synthesis in CIITA-transfected NB cells. Altogether, these data point to multiple mechanisms preventing HLA class II expression in the neuroblastoma, either involving CIITA promoter-IV silencing, or acting at the CIITA post-transcriptional level.

Original languageEnglish
Pages (from-to)7848-7857
Number of pages10
JournalOncogene
Volume22
Issue number49
DOIs
Publication statusPublished - Oct 30 2003

Fingerprint

Neuroblastoma
Interferons
Transcriptional Activation
Transfection
Cell Line
Messenger RNA
Confocal Microscopy
Transcription Factors
Complementary DNA
Western Blotting
DNA
Genes
Proteins

Keywords

  • CIITA
  • HLA class II
  • Neuroblastoma
  • Promoter methylation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Different levels of control prevent interferon-γ-inducible HLA-class II expression in human neuroblastoma cells. / Croce, Michela; De Ambrosis, Alessandro; Corrias, Maria V.; Pistoia, Vito; Occhino, Marzia; Meazza, Raffaella; Giron-Michel, Julien; Azzarone, Bruno; Accolla, Roberto S.; Ferrini, Silvano.

In: Oncogene, Vol. 22, No. 49, 30.10.2003, p. 7848-7857.

Research output: Contribution to journalArticle

Croce, M, De Ambrosis, A, Corrias, MV, Pistoia, V, Occhino, M, Meazza, R, Giron-Michel, J, Azzarone, B, Accolla, RS & Ferrini, S 2003, 'Different levels of control prevent interferon-γ-inducible HLA-class II expression in human neuroblastoma cells', Oncogene, vol. 22, no. 49, pp. 7848-7857. https://doi.org/10.1038/sj.onc.1207054
Croce, Michela ; De Ambrosis, Alessandro ; Corrias, Maria V. ; Pistoia, Vito ; Occhino, Marzia ; Meazza, Raffaella ; Giron-Michel, Julien ; Azzarone, Bruno ; Accolla, Roberto S. ; Ferrini, Silvano. / Different levels of control prevent interferon-γ-inducible HLA-class II expression in human neuroblastoma cells. In: Oncogene. 2003 ; Vol. 22, No. 49. pp. 7848-7857.
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AU - Occhino, Marzia

AU - Meazza, Raffaella

AU - Giron-Michel, Julien

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AB - The HLA class II expression is controlled by the transcriptional activator CIITA. The transcription of CIITA is controlled by different promoters, among which promoter-IV is inducible by IFN-γ. We analysed the regulation of HLA class II molecules by IFN-γ in a large series of human neuroblastoma cell lines. No induction of surface or intracellular HLA class II molecules and of specific mRNA was observed, in all neuroblastomas, with the exception of a nonprototypic cell line, ACN. In a large subset of neuroblastomas IFN-γ induced expression of CIITA mRNA, derived from promoter-IV, which was not methylated. In contrast, in another subset of neuroblastomas, CIITA was not inducible by IFN-γ and CIITA promoter-IV was either completely or partially methylated. Interestingly, the use of DNA demethylating agents restored CIITA gene transcriptional activation by IFN-γ, but not HLA class II expression. The defect of HLA class II was not related to alterations in RFX or NF-Y transcription factors, as suggested by EMSA or RFX gene transfection experiments. In addition, the transfection of a functional CIITA cDNA failed to induce HLA class II expression in typical neuroblastoma cells. Confocal microscopy and Western blot analysis suggested a defective nuclear translocation and/or reduced protein synthesis in CIITA-transfected NB cells. Altogether, these data point to multiple mechanisms preventing HLA class II expression in the neuroblastoma, either involving CIITA promoter-IV silencing, or acting at the CIITA post-transcriptional level.

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