PLX006366

GSE109570: Distinct Roles of BET Family Members in ER Enhancer Function and Gene Regulation in Breast Cancer Cells [RNA-seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Estrogen (E2)-dependent gene regulation mediated by estrogen receptor alpha (ER) plays a mitogenic role in ER-positive breast cancer cells. Although clinical applications of selective estrogen receptor modulators (SERMs), which directly interact with ER to alter ER activity, have been effective as a first line of treatment for breast cancer patients, a large subset of the patients will develop resistance after prolonged use of SERMs. Thus, there is a great need to develop alternative therapeutic strategies for SERM-resistant breast cancers. Here, we describe the potential use of the bromodomain family member protein (BRD) selective bromodomain inhibitor, JQ1, to alter E2-dependent gene expression program and inhibit E2-dependent growth of breast cancer cells. We show that each family member has partially redundant roles as ER coregulators that are required for ER-mediated gene transcription. Furthermore, we demonstrate the function of BRD3 as a molecular sensor of total BRD activity by the compensatory control of its protein levels. In addition, BRD3 colocalizes with a subset of ER binding sites (ERBSs) that are enriched for active enhancer features and associated with highly E2-induced genes. Collectively, we illustrate a critical role of the BET family members in ER dependent gene expression. SOURCE: W. Lee Kraus (lee.kraus@utsouthwestern.edu) - UT Southwestern Medical Center