Related Experiment Video

Updated: May 25, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

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

Published on: December 19, 2018

A role for estrogen receptor phosphorylation in the resistance to tamoxifen

Renée de Leeuw1, Jacques Neefjes, Rob Michalides

  • 1Department of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.

International Journal of Breast Cancer
|February 2, 2012
PubMed

Insights

Tamoxifen resistance in estrogen receptor-positive breast cancer is linked to estrogen receptor alpha (ERα) phosphorylation. Understanding these kinase pathways may predict treatment response and personalize therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of human cases.
  • Tamoxifen is the primary treatment, but resistance develops in about half of patients.
  • Few laboratory mechanisms of tamoxifen resistance have clinical application.

Purpose of the Study:

  • To highlight the role of estrogen receptor (ER) phosphorylation in tamoxifen resistance.
  • To discuss molecular pathways and kinases involved in ERα phosphorylation.
  • To explore clinical translation for predicting tamoxifen response.

Main Methods:

  • Review of molecular pathways and kinases mediating ERα phosphorylation.
  • Analysis of how ERα phosphorylation impacts tamoxifen resistance.
  • Discussion of clinical translation strategies.

Main Results:

  • Phosphorylation of ERα by various kinases at specific sites is a key mechanism of tamoxifen resistance.
  • Specific molecular pathways and kinases contribute to ERα phosphorylation and subsequent resistance.
  • Potential exists for predicting tamoxifen response based on tumor sample analysis.

Conclusions:

  • ERα phosphorylation is a critical factor in tamoxifen resistance.
  • Understanding these mechanisms can lead to personalized breast cancer treatment.
  • Clinical translation may enable prediction of tamoxifen efficacy before treatment.

More Related Videos

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer10:36

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

Published on: March 17, 2016

An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation08:48

An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation

Published on: June 30, 2015

Related Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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:
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...