These authors contributed equally to this work.
Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells
Article first published online: 22 JUN 2011
© 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 37, Issue 4, pages 381–394, June 2011
How to Cite
Orzan, F., Pellegatta, S., Poliani, P. L., Pisati, F., Caldera, V., Menghi, F., Kapetis, D., Marras, C., Schiffer, D. and Finocchiaro, G. (2011), Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells. Neuropathology and Applied Neurobiology, 37: 381–394. doi: 10.1111/j.1365-2990.2010.01132.x
- Issue published online: 22 JUN 2011
- Article first published online: 22 JUN 2011
- Accepted manuscript online: 8 OCT 2010 01:09AM EST
- Received 12 February 2010 , Accepted after revision 2 October 2010 , Published online Article Accepted on 8 October 2010
- glioma stem-like cells;
F. Orzan, S. Pellegatta, P. L. Poliani, F. Pisati, V. Caldera, F. Menghi, D. Kapetis, C. Marras, D. Schiffer and G. Finocchiaro (2011) Neuropathology and Applied Neurobiology37, 381–394 Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells
Aims: Proteins of the Polycomb repressive complex 2 (PRC2) are epigenetic gene silencers and are involved in tumour development. Their oncogenic function might be associated with their role in stem cell maintenance. The histone methyltransferase Enhancer of Zeste 2 (EZH2) is a key member of PRC2 function: we have investigated its expression and function in gliomas. Methods:EZH2 expression was studied in grade II–IV gliomas and in glioma stem-like cells (GSC) by quantitative PCR and immunohistochemistry. Effects of EZH2 down-regulation were analysed by treating GSC with the histone deacetylase (HDAC) inhibitor suberoylanide hydroxamic acid (SAHA) and by shRNA. Results: DNA microarray analysis showed that EZH2 is highly expressed in murine and human GSC. Real-time PCR on gliomas of different grade (n = 66) indicated that EZH2 is more expressed in glioblastoma multiforme (GBM) than in low-grade gliomas (P = 0.0013). This was confirmed by immunohistochemistry on an independent set of 106 gliomas. Treatment with SAHA caused significant up-regulation of PRC2 predicted target genes, GSC disruption and decreased expression of EZH2 and of the stem cell marker CD133. Inhibition of EZH2 expression by shRNA was associated with a significant decrease of glioma proliferation. Conclusion: The data suggest that EZH2 plays a role in glioma progression and encourage the therapeutic targeting of these malignancies by HDAC inhibitors.