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Updated: Jun 23, 2026
06:07
Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay
Published on: June 7, 2020
The silent estrogen receptor--can we make it speak?
Madhavi Billam1, Abigail E Witt, Nancy E Davidson
1The Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University, 1650 Orleans St., Baltimore, MD 21231, USA.
Cancer Biology & Therapy
|May 5, 2009
Summary
Breast cancer is often hormone-dependent, but resistance to endocrine therapy is common. Silencing of estrogen receptor alpha (ERα) is a key mechanism of this resistance, offering potential therapeutic targets.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Breast cancer is a prevalent women's cancer, often dependent on hormones.
- Estrogen receptor alpha (ERα) expression predicts prognosis and response to endocrine therapy in about two-thirds of cases.
- Current therapies targeting estrogen signaling include tamoxifen, fulvestrant, aromatase inhibitors, and LHRH agonists.
Purpose of the Study:
- To explore mechanisms of endocrine resistance in breast cancer.
- To focus on the silencing of ERα expression as a resistance mechanism.
- To investigate clinical exploitation of ERα silencing.
Main Methods:
- Review of molecular and biological advances in understanding endocrine resistance.
- Focus on ERα silencing as a specific mechanism.
- Exploration of clinical applications related to ERα silencing.
Main Results:
- Hormonal factors significantly influence breast cancer development, progression, and metastasis.
- Approximately 60% of ERα-positive breast cancers respond to hormonal therapy.
- Tumors lacking ERα and progesterone receptor (PgR) expression are resistant to hormone therapy.
Conclusions:
- Endocrine resistance, including acquired or de novo resistance, is a significant challenge in breast cancer treatment.
- Silencing of ERα expression is a key mechanism contributing to endocrine resistance.
- Understanding ERα silencing may lead to novel clinical strategies for overcoming endocrine resistance.
Related Concept Videos
01:45Endocrine Signaling
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
01:45Endocrine Signaling
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:33Hormonal Regulation
The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
01:40Hormonal Regulation
Hormones regulate a significant portion of digestion through activation of the neuroendocrine system. The neuroendocrine system of digestion contains many different hormones all with multiple functions that are both, directly and indirectly, involved in digestion.
01:08Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell