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Characterization of signaling function and expression of HLA class I molecules in medulloblastoma


Smith, C; Santi, M; Rushing, E J; Cornelison, R; MacDonald, T J; Vukmanovic, S (2011). Characterization of signaling function and expression of HLA class I molecules in medulloblastoma. Journal of Neuro-Oncology, 103(2):197-206.

Abstract

Although known for the important function in the immune system, MHC class I molecules are increasingly ascribed an alternative role in modifying signal transduction. In medulloblastoma, HLA class I molecules are associated with poor prognosis, and can induce ERK1/2 activation upon engagement with ligands that bind to incompletely assembled complexes (so called open conformers). We here demonstrate that ERK1/2 activation in medulloblastoma can occur in the absence of endogenously synthesized β2m, formally excluding involvement of closed HLA class conformation. In addition, several experimental observations suggest that heterogeneity of HLA class I expression may be a reflection of the status of original cells before transformation, rather than a consequence of immune-based selection of HLA-loss mutants. These results contribute to our understanding of an immune system-independent role of HLA class I in the pathology of medulloblastoma, and cancer in general.

Although known for the important function in the immune system, MHC class I molecules are increasingly ascribed an alternative role in modifying signal transduction. In medulloblastoma, HLA class I molecules are associated with poor prognosis, and can induce ERK1/2 activation upon engagement with ligands that bind to incompletely assembled complexes (so called open conformers). We here demonstrate that ERK1/2 activation in medulloblastoma can occur in the absence of endogenously synthesized β2m, formally excluding involvement of closed HLA class conformation. In addition, several experimental observations suggest that heterogeneity of HLA class I expression may be a reflection of the status of original cells before transformation, rather than a consequence of immune-based selection of HLA-loss mutants. These results contribute to our understanding of an immune system-independent role of HLA class I in the pathology of medulloblastoma, and cancer in general.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:08 Jan 2012 09:42
Last Modified:05 Apr 2016 15:17
Publisher:Springer
ISSN:0167-594X
Publisher DOI:10.1007/s11060-010-0378-3
PubMed ID:20811766
Permanent URL: http://doi.org/10.5167/uzh-53651

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