Inhibition of enhancer of zest homologue 2 is a potential therapeutic target for high‐MYC medulloblastoma

• DOI: 10.1111/neup.12534
• Publication Date: 2019-01-11T10:14:07Z
• Authors: Manabu Natsumeda; Yang Liu; Satoshi Nakata; Hiroaki Miyahara; Allison Hanaford; Sama Ahsan; Duncan Stearns; Nicolas Skuli; Ulf D. Kahlert; Eric H. Raabe; Fausto J. Rodriguez; Charles G. Eberhart
• Keywords: Proto-Oncogene Proteins c-myc; 0301 basic medicine; 03 medical and health sciences; Cell Line, Tumor; Gene Knockdown Techniques; Humans; Apoptosis; Enhancer of Zeste Homolog 2 Protein; Enzyme Inhibitors; Cerebellar Neoplasms; Medulloblastoma; 3. Good health

MYC amplification is common in Group 3 medulloblastoma and associated with poor survival. 4 medulloblastomas are also known to have elevated levels of histone H3-lysine 27-tri-methylation (H3K27me3), at least part due high expression the H3K27 methyltransferase enhancer zest homologue 2 (EZH2), which can be regulated by MYC. We therefore examined whether EZH2 H3K27me3 medulloblastoma, if high-MYC particularly sensitive pharmacological blockade. Western blot analysis low (DAOY, UW228, CB SV40) (DAOY-MYC, UW228-MYC, CB-MYC, D425) cell lines showed that higher were In fixed samples using immunohistochemistry, most positive tumors had H3K27me3, but many negative ones did as well, correlation was not statistically significant. All tested inhibitor EPZ6438. Many grew more slowly presence EPZ6438, although DAOY-MYC cells responded strongly than parent DAOY cultures lower levels. find increased EZH2, blockade a potential therapeutic strategy for aggressive