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Thyroid Hormone Receptor Beta Competes with Estrogen Receptor Alpha to Regulate the Transcriptome in ER+ Breast Cancer Cells
McFarland, Sydney A
McFarland, Sydney A
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Breast cancer (BCa) is the most diagnosed cancer in women worldwide, and treatment options are determined by hormone receptor status. Estrogen receptor positive (ER+) BCa is characterized by the tumor promoter estrogen receptor alpha (ERα) and is receptive to hormone therapies. However, current hormone therapies don’t prevent remission in patients and can result in drug resistance in up to 40% of ER+ BCa patients, which highlights the need for novel therapeutic options. The Carr lab focuses on the tumor suppressor thyroid hormone receptor beta (TRβ) and its therapeutic potential in ER+ BCa. TRβ and ERα regulate a common set of genes and have been found in complexes with several common proteins, such as the lysine-specific demethylase 1 (LSD1), despite their differing actions. In this study, we demonstrated that ERα, LSD1, and TRb exist within the same complex. Furthermore, the activation of TRβ with endogenous thyroid hormone or the TRβ-selective drug sobetirome (GC-1) in combination with estrogen hormone may alter these protein-protein interactions and their ability to bind to DNA. Finally, this study began an investigation into the transcriptomic profile of ER+ BCa cells treated with GC-1 or T3 to understand the impact of these treatments on global gene expression. These findings contribute to our understanding of TRβ and ERα competition in BCa, and the molecular mechanisms behind the proposed BCa therapeutic GC-1.
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2024-01-01
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McFarland_Thesis_.pdf
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