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Chromatin Dynamics of Endocrine Disruptor Compounds on Estrogen Receptor Function

内分泌干扰物化合物对雌激素受体功能的染色质动态

基本信息

批准号：
8616375
负责人：
Craig J Burd
金额：
$ 24.32万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8616375
关键词：
Address Affect Animal Model Binding Biochemical Biological Breast Breast Cancer Cell Cancer Patient Cells Cessation of life Characteristics Chemicals Chromatin Chromatin Structure Data Development Diagnosis Disease Endocrine Disruptors Environmental Estrogen Epigenetic Process Estradiol Estrogen Antagonists Estrogen Receptors Estrogen Therapy Estrogen receptor positive Estrogens Event Exhibits Exposure to Formaldehyde Gene Expression Profile Gene Targeting Genetic Transcription Genistein Genomics Glucocorticoid Receptor Growth Histone Deacetylation Hyperplasia Individual Lesion Ligands Long-Term Effects Malignant Neoplasms Mammary Neoplasms Mission Modeling Modification Monitor National Institute of Environmental Health Sciences Nuclear Receptors Nuclear Translocation Nucleosomes Physiological Plants Play Positioning Attribute Receptor Activation Receptor Gene Recruitment Activity Regulation Regulatory Element Research Response Elements Risk Risk Factors Role Signal Transduction Techniques United States Woman Work bisphenol A chromatin modification endocrine disruptor exposure epigenome genome-wide high risk histone methyltransferase histone modification hormone therapy human disease in vivo insight malignant breast neoplasm postnatal prenatal programs receptor receptor function response tumorigenesis

项目摘要

A woman's overall lifetime exposure to estrogen is a critical risk factor for the development of breast cancer. A number of environmental compounds, termed endocrine disrupting compounds (EDCs) have been shown to bind and activate the estrogen receptor and are thus implicated in breast cancer tumorigenesis. However, it has become clear that EDC activation of the estrogen receptor induces ligand-specific transcriptional programs. It is our hypothesis that chromatin structure is a key regulator of endocrine, disruptor action in breast cancer development and progression. In this proposal, we will use an unbiased genomic approach to characterize chromatin structure in breast cancer cells following treatment with bisphenol A and genistein. EDC responsive regions will be characterized for chromatin modifications and nucleosome positioning. Finally, the effects of long term exposure to both bisphenol A and genistein on estrogen receptor recruitment will be examined. These studies will clarify the mechanisms by which EDCs elicit specific transcriptional profiles in the breast.

女性一生中暴露于雌激素是乳腺癌发展的一个关键风险因素。许多环境化合物，称为内分泌干扰化合物（EDCs）已被证明结合并激活雌激素受体，因此与乳腺癌肿瘤发生有关。但是，在这方面，已经清楚的是，雌激素受体的EDC激活诱导配体特异性转录，程序.我们的假设是，染色质结构是内分泌干扰作用的关键调节因子，乳腺癌的发展和进展。在这个建议中，我们将使用一个公正的基因组方法，表征用双酚A和染料木黄酮处理后乳腺癌细胞中的染色质结构。将表征EDC响应区的染色质修饰和核小体定位。最后，长期暴露于双酚A和染料木素对雌激素受体募集的影响将被审查。这些研究将阐明内分泌干扰物引起特异性转录的机制，胸部的轮廓