Different levels of control prevent interferon-γ-inducible hla-class ii expression in human neuroblastoma cells

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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IMPLICATIONS FOR CANCER PROGRESSION Article Open access 22 April 2021 IL-10 TARGETS IRF TRANSCRIPTION FACTORS TO SUPPRESS IFN AND INFLAMMATORY RESPONSE GENES BY EPIGENETIC MECHANISMS Article

22 April 2025 HERITABLE MAINTENANCE OF CHROMATIN MODIFICATIONS CONFERS TRANSCRIPTIONAL MEMORY OF INTERFERON-Γ SIGNALING Article Open access 04 April 2025 REFERENCES * Accolla RS,

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and van den Elsen PJ . (2002). _Int. J. Cancer_, 97, 501–507. Download references ACKNOWLEDGEMENTS This work has been supported by grants awarded by the AIRC (Italian Association for Cancer

Research) and MIUR (Ministry of the University and Research). MO was supported by a fellowship from FIRC (Fondazione Italiana per la Ricerca sul Cancro) and MC from Italian Neuroblastoma

Association. AUTHOR INFORMATION Author notes * Michela Croce and Alessandro De Ambrosis: Both contributed equally to this work. AUTHORS AND AFFILIATIONS * Istituto Nazionale per la Ricerca

sul Cancro, Genoa, 16132, Italy Michela Croce, Alessandro De Ambrosis & Silvano Ferrini * Istituto G Gaslini, Genoa, 16147, Italy Maria V Corrias, Vito Pistoia, Marzia Occhino & 

Raffaella Meazza * Dipartimento di Scienze Cliniche e Biologiche, Università dell'Insubria, 21100, Varese, Italy Raffaella Meazza & Roberto S Accolla * U 506 INSERM, Hôpital Paul

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AUTHOR Correspondence to Silvano Ferrini. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Croce, M., De Ambrosis, A., Corrias, M. _et al._ Different

levels of control prevent interferon-_γ_-inducible HLA-class II expression in human neuroblastoma cells. _Oncogene_ 22, 7848–7857 (2003). https://doi.org/10.1038/sj.onc.1207054 Download

citation * Received: 16 December 2002 * Revised: 03 July 2003 * Accepted: 31 July 2003 * Published: 30 October 2003 * Issue Date: 30 October 2003 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * HLA class II * CIITA * neuroblastoma * promoter

methylation