Introduction: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by increased necrosis and intense resistance to therapy. Although, little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes, such as the Notch, EGFR and p53 pathways, seem to play an important role in the formation/maintenance of GBM.
Methods: Notch signaling is aberrantly activated in GBM and orchestrates the malignant traits of GBM, but current knowledge regarding the downstream players of Notch in GBM remains limited. Recently we have identified that Notch effector HEY1 is highly upregulated in hGBM (human) surgical biopsies and its overexpression appears to be correlative with high-grade glioma. Our immunoblot experiments revealed that HEY1 expression significantly correlated with O6-alkylguanine DNA alkyltransferase (MGMT) levels in hGBM specimens.
Results: The inhibition of HEY1 reduced invasive, migratory and proliferative abilities of GBM cells, in vitro. Furthermore, our experiments with TF-TF; TF-DNA arrays conducted using recombinant HEY1 showed its interaction with multiple transcription factors emphasizing its importance in GBM, highlighting HEY1 as a potential therapeutic target that can be evaluated in GBM.
Conclusions: These data obtained help us on delineating the role of HEY1 in regulating GBM
tumor growth and progression.
Patient Care: Implication of larger array of potential targets are to be studied for therapeutic purpose to improve our current understanding of the mechanistic insight required to translate these therapies into clinical treatment paradigms.
Learning Objectives: Implication of larger array of potential targets are to be studied for therapeutic purpose to improve our current understanding of the mechanistic insight required to translate these therapies into clinical treatment paradigms.
References: Gaetani P, Hulleman E, Levi D, et al., Expression of the transcription factor HEY1 in glioblastoma: a preliminary clinical study.Tumori. 2010 Jan-Feb;96(1):97-102.
Hulleman E, Quarto M, Vernell R, et al., A role for the transcription factor HEY1 in
glioblastoma. J Cell Mol Med. 2009 Jan;13(1):136-46.