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A role for the transcription factor HEY1 in glioblastoma

Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes, such as...

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Autores principales: Hulleman, Esther, Quarto, Micaela, Vernell, Richard, Masserdotti, Giacomo, Colli, Elena, Kros, Johan M, Levi, Daniel, Gaetani, Paolo, Tunici, Patrizia, Finocchiaro, Gaetano, Baena, Riccardo Rodriguez y, Capra, Maria, Helin, Kristian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823042/
https://www.ncbi.nlm.nih.gov/pubmed/18363832
http://dx.doi.org/10.1111/j.1582-4934.2008.00307.x
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author Hulleman, Esther
Quarto, Micaela
Vernell, Richard
Masserdotti, Giacomo
Colli, Elena
Kros, Johan M
Levi, Daniel
Gaetani, Paolo
Tunici, Patrizia
Finocchiaro, Gaetano
Baena, Riccardo Rodriguez y
Capra, Maria
Helin, Kristian
author_facet Hulleman, Esther
Quarto, Micaela
Vernell, Richard
Masserdotti, Giacomo
Colli, Elena
Kros, Johan M
Levi, Daniel
Gaetani, Paolo
Tunici, Patrizia
Finocchiaro, Gaetano
Baena, Riccardo Rodriguez y
Capra, Maria
Helin, Kristian
author_sort Hulleman, Esther
collection PubMed
description Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically up-regulated in glioma and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally, we show that ectopic expression of HEY1 induces cell proliferation in neural stem cells, while depletion of HEY1 by RNA interference reduces proliferation of glioblastoma cells in tissue culture. Together, these data imply a role for HEY1 in the progression of GBM, and therefore we propose that HEY1 may be a therapeutic target for glioblastoma patients. Moreover, HEY1 may represent a molecular marker to distinguish GBM patients with a longer survival prognosis from those at high risk.
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spelling pubmed-38230422015-04-27 A role for the transcription factor HEY1 in glioblastoma Hulleman, Esther Quarto, Micaela Vernell, Richard Masserdotti, Giacomo Colli, Elena Kros, Johan M Levi, Daniel Gaetani, Paolo Tunici, Patrizia Finocchiaro, Gaetano Baena, Riccardo Rodriguez y Capra, Maria Helin, Kristian J Cell Mol Med Articles Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically up-regulated in glioma and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally, we show that ectopic expression of HEY1 induces cell proliferation in neural stem cells, while depletion of HEY1 by RNA interference reduces proliferation of glioblastoma cells in tissue culture. Together, these data imply a role for HEY1 in the progression of GBM, and therefore we propose that HEY1 may be a therapeutic target for glioblastoma patients. Moreover, HEY1 may represent a molecular marker to distinguish GBM patients with a longer survival prognosis from those at high risk. Blackwell Publishing Ltd 2009-01 2008-03-17 /pmc/articles/PMC3823042/ /pubmed/18363832 http://dx.doi.org/10.1111/j.1582-4934.2008.00307.x Text en © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Articles
Hulleman, Esther
Quarto, Micaela
Vernell, Richard
Masserdotti, Giacomo
Colli, Elena
Kros, Johan M
Levi, Daniel
Gaetani, Paolo
Tunici, Patrizia
Finocchiaro, Gaetano
Baena, Riccardo Rodriguez y
Capra, Maria
Helin, Kristian
A role for the transcription factor HEY1 in glioblastoma
title A role for the transcription factor HEY1 in glioblastoma
title_full A role for the transcription factor HEY1 in glioblastoma
title_fullStr A role for the transcription factor HEY1 in glioblastoma
title_full_unstemmed A role for the transcription factor HEY1 in glioblastoma
title_short A role for the transcription factor HEY1 in glioblastoma
title_sort role for the transcription factor hey1 in glioblastoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823042/
https://www.ncbi.nlm.nih.gov/pubmed/18363832
http://dx.doi.org/10.1111/j.1582-4934.2008.00307.x
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