Cargando…
Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma
In Hodgkin lymphoma (HL) we recently identified deregulated expression of homeobox genes MSX1 and OTX2 which are physiologically involved in development of the embryonal neural plate border region. Here, we examined in HL homeobox gene SIX1 an additional regulator of this embryonal region mediating...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741883/ https://www.ncbi.nlm.nih.gov/pubmed/26473286 |
_version_ | 1782414091845894144 |
---|---|
author | Nagel, Stefan Meyer, Corinna Kaufmann, Maren Drexler, Hans G. MacLeod, Roderick A.F. |
author_facet | Nagel, Stefan Meyer, Corinna Kaufmann, Maren Drexler, Hans G. MacLeod, Roderick A.F. |
author_sort | Nagel, Stefan |
collection | PubMed |
description | In Hodgkin lymphoma (HL) we recently identified deregulated expression of homeobox genes MSX1 and OTX2 which are physiologically involved in development of the embryonal neural plate border region. Here, we examined in HL homeobox gene SIX1 an additional regulator of this embryonal region mediating differentiation of placodal precursors. SIX1 was aberrantly activated in 12 % of HL patient samples in silico, indicating a pathological role in a subset of this B-cell malignancy. In addition, SIX1 expression was detected in HL cell lines which were used as models to reveal upstream factors and target genes of this basic developmental regulator. We detected increased copy numbers of the SIX1 locus at chromosome 14q23 correlating with enhanced expression while chromosomal translocations were absent. Moreover, comparative expression profiling data and pertinent gene modulation experiments indicated that the WNT-signalling pathway and transcription factor MEF2C regulate SIX1 expression. Genes encoding the transcription factors GATA2, GATA3, MSX1 and SPIB – all basic lymphoid regulators - were identified as targets of SIX1 in HL. In addition, cofactors EYA1 and TLE4, respectively, contrastingly mediated activation and suppression of SIX1 target gene expression. Thus, the protein domain interfaces may represent therapeutic targets in SIX1-positive HL subsets. Collectively, our data reveal a gene regulatory network with SIX1 centrally deregulating lymphoid differentiation and support concordance of lymphopoiesis/lymphomagenesis and developmental processes in the neural plate border region. |
format | Online Article Text |
id | pubmed-4741883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47418832016-03-23 Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma Nagel, Stefan Meyer, Corinna Kaufmann, Maren Drexler, Hans G. MacLeod, Roderick A.F. Oncotarget Research Paper In Hodgkin lymphoma (HL) we recently identified deregulated expression of homeobox genes MSX1 and OTX2 which are physiologically involved in development of the embryonal neural plate border region. Here, we examined in HL homeobox gene SIX1 an additional regulator of this embryonal region mediating differentiation of placodal precursors. SIX1 was aberrantly activated in 12 % of HL patient samples in silico, indicating a pathological role in a subset of this B-cell malignancy. In addition, SIX1 expression was detected in HL cell lines which were used as models to reveal upstream factors and target genes of this basic developmental regulator. We detected increased copy numbers of the SIX1 locus at chromosome 14q23 correlating with enhanced expression while chromosomal translocations were absent. Moreover, comparative expression profiling data and pertinent gene modulation experiments indicated that the WNT-signalling pathway and transcription factor MEF2C regulate SIX1 expression. Genes encoding the transcription factors GATA2, GATA3, MSX1 and SPIB – all basic lymphoid regulators - were identified as targets of SIX1 in HL. In addition, cofactors EYA1 and TLE4, respectively, contrastingly mediated activation and suppression of SIX1 target gene expression. Thus, the protein domain interfaces may represent therapeutic targets in SIX1-positive HL subsets. Collectively, our data reveal a gene regulatory network with SIX1 centrally deregulating lymphoid differentiation and support concordance of lymphopoiesis/lymphomagenesis and developmental processes in the neural plate border region. Impact Journals LLC 2015-10-12 /pmc/articles/PMC4741883/ /pubmed/26473286 Text en Copyright: © 2015 Nagel et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Nagel, Stefan Meyer, Corinna Kaufmann, Maren Drexler, Hans G. MacLeod, Roderick A.F. Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma |
title | Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma |
title_full | Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma |
title_fullStr | Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma |
title_full_unstemmed | Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma |
title_short | Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma |
title_sort | aberrant expression of homeobox gene six1 in hodgkin lymphoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741883/ https://www.ncbi.nlm.nih.gov/pubmed/26473286 |
work_keys_str_mv | AT nagelstefan aberrantexpressionofhomeoboxgenesix1inhodgkinlymphoma AT meyercorinna aberrantexpressionofhomeoboxgenesix1inhodgkinlymphoma AT kaufmannmaren aberrantexpressionofhomeoboxgenesix1inhodgkinlymphoma AT drexlerhansg aberrantexpressionofhomeoboxgenesix1inhodgkinlymphoma AT macleodroderickaf aberrantexpressionofhomeoboxgenesix1inhodgkinlymphoma |