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Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle.
- Source :
-
The Journal of pathology [J Pathol] 2013 Aug; Vol. 230 (4), pp. 399-409. - Publication Year :
- 2013
-
Abstract
- Hodgkin's lymphoma is unusual among B cell lymphomas, in so far as the malignant Hodgkin/Reed-Sternberg (HRS) cells lack a functional B cell receptor (BCR), as well as many of the required downstream signalling components. In Epstein-Barr virus (EBV)-positive cases of Hodgkin's lymphoma, HRS cells express the viral latent membrane proteins (LMP)-1 and -2A. LMP2A is thought to contribute to the pathogenesis of Hodgkin's lymphoma by providing a surrogate BCR-like survival signal. However, LMP2A has also been shown to induce the virus-replicative cycle in B cells, an event presumably incompatible with lymphomagenesis. In an attempt to resolve this apparent paradox, we compared the transcriptional changes observed in primary HRS cells with those induced by LMP2A and by BCR activation in primary human germinal centre (GC) B cells, the presumed progenitors of HRS cells. We found a subset of genes that were up-regulated by both LMP2A expression and BCR activation but which were down-regulated in primary HRS cells. These genes included EGR1, an immediate-early gene that is required for BCR-induced entry to the virus-replicative cycle. We present data supporting a model for the pathogenesis of EBV-positive Hodgkin's lymphoma in which LMP2A-expressing HRS cells lacking BCR signalling functions cannot induce EGR1 and are consequently protected from entry to the virus lytic cycle. The primary microarray data are available from GEO (http://www.ncbi.nlm.nih.gov/geo/) under series Accession No 46143.<br /> (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Subjects :
- B-Lymphocytes metabolism
Burkitt Lymphoma metabolism
Burkitt Lymphoma pathology
Burkitt Lymphoma virology
Cell Line, Tumor
Cytopathogenic Effect, Viral
Early Growth Response Protein 1 genetics
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases metabolism
Gene Expression Profiling methods
Gene Expression Regulation, Neoplastic
Herpesvirus 4, Human genetics
Herpesvirus 4, Human pathogenicity
Hodgkin Disease genetics
Hodgkin Disease pathology
Hodgkin Disease virology
Humans
Oligonucleotide Array Sequence Analysis
Receptors, Antigen, B-Cell metabolism
Reed-Sternberg Cells pathology
Reed-Sternberg Cells virology
Trans-Activators metabolism
Transfection
Up-Regulation
Viral Matrix Proteins genetics
Early Growth Response Protein 1 metabolism
Herpesvirus 4, Human metabolism
Hodgkin Disease metabolism
Reed-Sternberg Cells metabolism
Viral Matrix Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9896
- Volume :
- 230
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23592216
- Full Text :
- https://doi.org/10.1002/path.4198