Related Experiment Video

Updated: May 1, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

23.1K

ERK/MAPK regulates ERRγ expression, transcriptional activity and receptor-mediated tamoxifen resistance in ER+ breast

Mary M Heckler1, Hemang Thakor, Cara C Schafer

  • 1Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA.

The FEBS Journal
|April 2, 2014
PubMed

Insights

Estrogen-related receptor gamma (ERRγ) promotes tamoxifen resistance in breast cancer. Kinase regulation of ERRγ, specifically via ERK/MAPK signaling, impacts its activity and tamoxifen resistance, offering new therapeutic insights.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Selective estrogen receptor modulators like tamoxifen (TAM) improve survival for ER+ breast cancer.
  • TAM resistance is a significant clinical challenge, often driven by altered signaling pathways rather than estrogen receptor mutations.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of Estrogen-related receptor gamma (ERRγ) and its role in TAM resistance.
  • To investigate the impact of kinase signaling on ERRγ function in ER+ breast cancer.

Main Methods:

  • Quantitative reverse transcription PCR (RT-PCR) and Western blotting for gene and protein analysis.
  • Site-directed mutagenesis to assess extracellular signal-regulated kinase (ERK) target sites.
  • Flow cytometry for cell proliferation and cell-cycle analysis; dual-luciferase assays for transcriptional activity.

Main Results:

  • ERRγ protein levels are modulated by the activation status of ERK/mitogen-activated protein kinase (MAPK).
  • Disruption of ERK target sites on ERRγ reduced its transcriptional activity and tamoxifen resistance.
  • Kinase regulation of ERRγ directly influences its role in promoting TAM resistance.

Conclusions:

  • Estrogen-related receptor gamma (ERRγ) is regulated by kinase signaling, specifically ERK/MAPK.
  • This kinase regulation is crucial for ERRγ's contribution to tamoxifen resistance in ER+ breast cancer.
  • Findings reveal a novel mechanism of nuclear receptor regulation and its implication in endocrine therapy resistance.
Keywords:
ER+ breast cancerERK/MAPKestrogen-related receptor γtamoxifentranscription

More Related Videos

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

11.6K
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

9.7K

Related Concept Videos

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...
6.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.1K
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...
3.6K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.7K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
81