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Breast cancer cell lines treated with EZH2 inhibitor compounds

ABSTRACT: Loss of H3K27me3 repressive chromatin histone marks, maintained by the histone methyltransferase (HKMT) EZH2, may lead to reversal of epigenetic silencing in tumor cells and have therapeutic potential. Using a cell-based assay, we have identified three compounds from a HKMT inhibitor chemical library which re-express H3K27me3 mediated, silenced genes. Chromatin immunoprecipitation verified a decrease in silencing marks (H3K27me3, H3K9me3) and importantly an increase in active marks (H3K4me2/3, H3K27ac) at the promoter of re-expressed genes. Compound treated breast tumor cells induced enrichment for genome-wide changes in expression of known target genes for EZH2 and induced cell growth inhibition: with most sensitive breast tumor cell lines having low EZH2 protein expression, while a normal epithelial breast line was least sensitive. Agilent SurePrint G3 Human 8x60k two-colour microarrays were used to profile gene expression changes induced by treatment with drug compounds in MDA MB-231 cells, both at 24h and 48h. 4 replicates were used for each drug, time combination. A separate untreated control sample was used for comparison with each replicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Ed Curry

PROVIDER: E-GEOD-36131 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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