Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells

被引：107
作者：
Orzan, F. [1 ]
Pellegatta, S. [1 ,2 ]
Poliani, P. L. [4 ]
Pisati, F. [1 ,2 ]
Caldera, V.
Menghi, F. [6 ]
Kapetis, D. [3 ]
Marras, C. [1 ]
Schiffer, D. [5 ]
Finocchiaro, G. [1 ,2 ]
机构：
[1] Univ Milano Bicocca, Fdn IRCCS, Ist Neurol C Besta, I-20133 Milan, Italy
[2] Univ Milano Bicocca, IFOM IEO Campus, I-20133 Milan, Italy
[3] Univ Milano Bicocca, Genopolis Consortium Funct Gen, I-20133 Milan, Italy
[4] Univ Brescia, Brescia, Italy
[5] Ctr Ric Neurobiooncol, Vercelli, Italy
[6] NHS Trust, Great Ormond St Hosp Children, London, England
来源：
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY | 2011年 / 37卷 / 04期
关键词：
CD133; EZH2; glioblastoma; glioma stem-like cells; HDAC; Polycomb; SUBEROYLANILIDE HYDROXAMIC ACID; GENE-EXPRESSION; IN-VITRO; CANCER; DIFFERENTIATION; INHIBITORS; GROWTH; TUMORS; SAHA; VIVO;
D O I：
10.1111/j.1365-2990.2010.01132.x
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
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.
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页码：381 / 394
页数：14
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