Abstract 1470: Characterization of ER receptor transcription complex using super resolution STORM microscopy

Abstract

Abstract Steroid/thyroid hormone receptors are ligand-dependent transcription factors (TFs) that play fundamental roles in cell development and homeostasis. They bind to their DNA response elements and modulate the transcription of target genes via interaction with co-regulators termed co-activators or co-repressors. Estrogen Receptor α (ERα) is an important member of this family which is expressed in in hormone receptor positive (ER+) breast cancer, one of the leading causes of death among women. Current therapeutic options involve endocrine therapies, however despite its effectiveness, a significant number of patients eventually experience resistance to these treatments, leading to disease recurrence and relapse. One of the major hurdles to combat resistant cells, is lack of comprehensive information about ERα transcriptional complex activity. While biochemical assays have provided significant information on interaction with its coregulators, it is not clear how the dynamic between these transpire. This is while ERα is a highly dynamic protein with a fast rate of interaction with coregulators and cycling between chromatin, nucleus, and cytosol. Consequently, it is critical to imply techniques that allow direct visualization of ERα activity and gain spatiotemporal information on its regulation. One of the major limitations to conduct such studies was due to the resolution limits inherited with light microscopes. However, the emerge of super resolution microscopes, offers a promising tool to overcome this challenge. Here, we imply super resolution microscopy to examine the mechanism of ERα transcriptional activity in the presence of estrogen as well as compounds that are currently used for endocrine therapy, Tamoxifen and Fulvestrant. We determine how each of these compounds influence ERα interaction with its co-activators (P300, SRC-3), and its co-inhibitor (NCoRI), and how these interactions modulate chromatin activity. Obtaining such information of ERα dynamics is critical to map the mechanism of its activity under different treatments, and thus is key to overcome some of the hurdles faced in endocrine therapy. Citation Format: Tara Akhshi, Myles Brown. Characterization of ER receptor transcription complex using super resolution STORM microscopy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1470.