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Appolloni, I.* ; Calzolari, F. ; Barilari, M.* ; Terrile, M.* ; Daga, A.* ; Malatesta, P.*

Antagonistic modulation of gliomagenesis by Pax6 and Olig2 in PDGF-induced oligodendroglioma.

Int. J. Cancer 131, E1078-E1087 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Gliomas are aggressive tumors of the central nervous system originating from proliferating neural cells. Regulators of neural stem or progenitor cells biology may thus influence aspects of brain tumorigenesis, such as the maintenance of tumor-propagating potential. We investigated the role of Pax6, a neurogenic transcription factor already suggested as a positive prognostic marker for human gliomas, in a well-characterized in vivo model of PDGF-B-driven oligodendroglioma. In this system, the expression of Pax6 severely impairs tumor propagation by inducing a reduction of cell proliferation and the acquisition of differentiation traits in tumor-initiating cells. The overexpression of Pax6 correlates with a downregulation of Olig2, a bHLH transcription factor that normally antagonizes Pax6 in adult neurogenic niches and that plays a key role in the maintenance of neural stem and progenitor cells. Furthermore, we found that Olig2 is strictly required to maintain the malignancy of oligodendroglioma cells, since its silencing by interfering RNA abrogates tumor propagation. We finally show evidence that this function depends, at least in part, on the silencing of ID4, a dominant negative bHLH protein, whose upregulation follows Olig2 loss. In our model, the upregulation of ID4 mimics the loss of Olig2 in impairing the tumor-propagating potential of glioma cells. Our data, therefore, establish the relevance of physiological regulators of neural stem cell biology in regulating glial tumor malignancy and provide support for their functional interactions in this context.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glioma; Neural stem cells; Neurogenesis; Gene silencing; Murine model
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Journal International Journal of Cancer
Quellenangaben Volume: 131, Issue: 7, Pages: E1078-E1087 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)