Related Experiment Video

Updated: Jun 2, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Estrogen receptor β: switching to a new partner and escaping from estrogen

Yuet-Kin Leung1, Shuk-Mei Ho

  • 1Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati Medical Center, Kettering Complex, Room 128, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH 45267, USA.

Science Signaling
|April 14, 2011
PubMed

Insights

Estrogen receptor beta (ERβ) suppresses prostate cancer, independent of 17β-estradiol. This receptor

Area of Science:

  • Molecular Endocrinology
  • Cancer Biology
  • Prostate Cancer Research

Background:

  • Estrogen receptor beta (ERβ) acts as a tumor suppressor in prostate cancer by inhibiting cell proliferation and promoting apoptosis.
  • The role of its presumed ligand, 17β-estradiol, in prostate cancer is paradoxical, as it can promote cancer development in experimental models.
  • The precise mechanisms governing the interaction between estrogens and ERβ in prostate cancer are not fully understood.

Purpose of the Study:

  • To investigate the mechanisms underlying the interplay between estrogens and ERβ in prostate cancer.
  • To explore the role of ERβ's tethering partner, Krüppel-like zinc finger transcription factor 5 (KLF5), and its downstream target FOXO1.
  • To determine the requirement of 17β-estradiol for ERβ's tumor-suppressive function in the prostate.

Main Methods:

  • Investigated the interaction between ERβ, KLF5, and FOXO1 in prostate cancer models.
  • Assessed the impact of 17β-estradiol on ERβ and KLF5-mediated signaling pathways.
  • Analyzed the functional consequences of these interactions on cell proliferation and apoptosis.

Main Results:

  • 17β-estradiol is not essential for ERβ's tumor-suppressive activity in the prostate, a tissue with limited estrogen.
  • The presence of 17β-estradiol diminishes ERβ- and KLF5-mediated signaling, paradoxically promoting cellular proliferation.
  • Identified KLF5 as a novel tethering partner of ERβ, influencing its function through downstream targets like FOXO1.

Conclusions:

  • ERβ's tumor-suppressive function in prostate cancer is estrogen-independent.
  • 17β-estradiol abrogates ERβ/KLF5 signaling, highlighting a complex role in cancer progression.
  • Future therapeutic strategies may leverage ERβ's estrogen-independent functions and nonclassical DNA binding via tethering partners.

More Related Videos

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer 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:
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Ending Relationships01:28

Ending Relationships

The dissolution of intimate relationships presents complex emotional and psychological challenges, particularly when emotional bonds are strong, the relationship is long-standing, and perceived alternatives are limited. This distress often intensifies in romantic breakups, where the initiator may experience greater turmoil than the rejected partner. Contributing factors include residual attachment, guilt over causing pain, and uncertainty about how to manage the situation. The stress is further...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Hormonal Regulation01:33

Hormonal 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.
Hormonal Regulation01:40

Hormonal 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.