A role for the transcription factor HEY1 in glioblastoma

Esther Hulleman, Micaela Quarto, Richard Vernell, Giacomo Masserdotti, Elena Colli, Johan M. Kros, Daniel Levi, Paolo Gaetani, Patrizia Tunici, Gaetano Finocchiaro, Riccardo Rodriguez Baena, Maria Capra, Kristian Helin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)136-146
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • E2F
  • Glioblastoma
  • HEY1
  • Molecular marker
  • Notch
  • RNA interference

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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  • Cite this

    Hulleman, E., Quarto, M., Vernell, R., Masserdotti, G., Colli, E., Kros, J. M., Levi, D., Gaetani, P., Tunici, P., Finocchiaro, G., Baena, R. R., Capra, M., & Helin, K. (2009). A role for the transcription factor HEY1 in glioblastoma. Journal of Cellular and Molecular Medicine, 13(1), 136-146. https://doi.org/10.1111/j.1582-4934.2008.00307.x