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Targeting the enhancer of zeste homologue 2 in medulloblastoma
Author(s) -
Alimova Irina,
Venkataraman Sujatha,
Harris Peter,
Marquez Victor E.,
Northcott Paul A.,
Dubuc Adrian,
Taylor Michael D.,
Foreman Nicholas K.,
Vibhakar Rajeev
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27455
Subject(s) - medulloblastoma , ezh2 , prc2 , biology , cancer research , histone h3 , enhancer , stem cell , cell growth , histone , transcription factor , microbiology and biotechnology , genetics , gene
Abstract Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 that catalyzes the trimethylation of histone H3 on Lys 27, and represses gene transcription. EZH2 enhances cancer‐cell proliferation and regulates stem cell maintenance and differentiation. Here, we demonstrate that EZH2 is highly expressed in medulloblastoma, a highly malignant brain tumor of childhood, and this altered expression is correlated with genomic gain of chromosome 7 in a subset of medulloblastoma. Inhibition of EZH2 by RNAi suppresses medulloblastoma tumor cell growth. We show that 3‐deazaneplanocin A, a chemical inhibitor of EZH2, can suppress medulloblastoma cell growth partially by inducing apoptosis. Suppression of EZH2 expression diminishes the ability of tumor cells to form spheres in culture and strongly represses the ability of known oncogenes to transform neural stem cells. These findings establish a role of EZH2 in medulloblastoma and identify EZH2 as a potential therapeutic target especially in high‐risk tumors.