Targeting the enhancer of zeste homologue 2 in medulloblastoma
Irina Alimova
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorSujatha Venkataraman
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorPeter Harris
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorVictor E. Marquez
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD
Search for more papers by this authorPaul A. Northcott
Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada
Search for more papers by this authorAdrian Dubuc
Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada
Search for more papers by this authorMichael D. Taylor
Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada
Search for more papers by this authorNicholas K. Foreman
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorCorresponding Author
Rajeev Vibhakar
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
MD, PhD, Department of Pediatrics University of Colorado Denver 12800 19th Ave Mail Stop 4103 Aurora, Colorado 80045Search for more papers by this authorIrina Alimova
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorSujatha Venkataraman
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorPeter Harris
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorVictor E. Marquez
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD
Search for more papers by this authorPaul A. Northcott
Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada
Search for more papers by this authorAdrian Dubuc
Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada
Search for more papers by this authorMichael D. Taylor
Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada
Search for more papers by this authorNicholas K. Foreman
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
Search for more papers by this authorCorresponding Author
Rajeev Vibhakar
Department of Pediatrics, The Children's Hospital and University of Colorado, Anschutz Medical Campus, CO
MD, PhD, Department of Pediatrics University of Colorado Denver 12800 19th Ave Mail Stop 4103 Aurora, Colorado 80045Search for more papers by this authorAbstract
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.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
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| IJC_27455_sm_SuppFigS1.eps266.7 KB | Supporting Information Figure 1. |
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| IJC_27455_sm_SuppFigS3.eps246.3 KB | Supporting Information Figure 3. |
| IJC_27455_sm_SuppFigS4.eps223.8 KB | Supporting Information Figure 4. |
| IJC_27455_sm_SuppFigS5.eps836 KB | Supporting Information Figure 5. |
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