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首页> 外文期刊>Journal of Cellular Physiology >Oncofetal Epigenetic Bivalency in Breast Cancer Cells: H3K4 and H3K27 Tri-Methylation as a Biomarker for Phenotypic Plasticity
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Oncofetal Epigenetic Bivalency in Breast Cancer Cells: H3K4 and H3K27 Tri-Methylation as a Biomarker for Phenotypic Plasticity

机译:瘤胎后生Bivalency乳腺癌细胞:H3K4和H3K27 Tri-Methylation作为生物标志物的表型可塑性

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摘要

Alterations in the epigenetic landscape are fundamental drivers of aberrant gene expression that contribute to cancer progression and pathology. Understanding specific modes of epigenetic regulation can be used to identify novel biomarkers or targets for therapeutic intervention to clinically treat solid tumors and leukemias. The bivalent marking of gene promoters by H3K4me3 and H3K27me3 is a primary mechanism to poise genes for expression in pluripotent embryonic stem cells (ESC). In this study we interrogated three well-established mammary cell lines to model epigenetic programming observed among breast cancer subtypes. Evidence is provided for a distinct bivalent signature, activating and repressive histone marks co-residing at the same gene promoter, in the MCF7 (ESR/PGR+) luminal breast cancer cell line. We identified a subset of genes, enriched for developmental pathways that regulate cellular phenotype and signaling, and partially recapitulate the bivalent character observed in ESC. We validated the biological relevance of this "oncofetal epigenetic" signature using data from ESR/PGR+ tumor samples from breast cancer patients. This signature of oncofetal epigenetic control is an informative biomarker and may provide novel therapeutic targets, selective for both recurring and treatment-resistant cancers. (C) 2016 Wiley Periodicals, Inc.
机译:在表观遗传改变景观异常基因表达的基本因素导致癌症恶化病理可以用来识别表观遗传调控新型生物标志物或治疗的目标临床治疗实体肿瘤和干预白血病。H3K4me3和H3K27me3是一个主要机制在多能风度的基因表达胚胎干细胞(ESC)。审问三的乳腺细胞行模型表观遗传编程在乳腺癌亚型。提供了一个独特的二价的签名,激活和压抑的组蛋白标记co-residing在同一基因启动子MCF7 (ESR / PGR +)腔的乳腺癌细胞系。我们确定了基因的一个子集,丰富发展途径调节细胞表型和信号,部分概括二价性格中观察到ESC。这种“瘤胎后生”签名使用数据从ESR / PGR +乳腺癌的肿瘤样本病人。控制是一个信息丰富的生物标志物和可能提供新的治疗靶点,选择性重复和难治性癌症。(C) 2016年威利期刊公司。

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