title: A role for the transcription factor HEY1 in glioblastoma.
abstract: 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.
authors: European Institute of Oncology, Via Ripamonti, Milan, Italy.
authors: Esther
authors: E
authors: Hulleman
authors: Micaela
authors: M
authors: Quarto
authors: Richard
authors: R
authors: Vernell
authors: Giacomo
authors: G
authors: Masserdotti
authors: Elena
authors: E
authors: Colli
authors: Johan M
authors: JM
authors: Kros
authors: Daniel
authors: D
authors: Levi
authors: Paolo
authors: P
authors: Gaetani
authors: Patrizia
authors: P
authors: Tunici
authors: Gaetano
authors: G
authors: Finocchiaro
authors: Riccardo Rodriguez Y
authors: RR
authors: Baena
authors: Maria
authors: M
authors: Capra
authors: Kristian
authors: K
authors: Helin
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D018450:Disease Progression; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D046888:Tissue Array Analysis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D050684:E2F Transcription Factors; D051880:Receptors, Notch; C485631:HEY1 protein, human