Related Experiment Video

Updated: Apr 28, 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

9.7K

An epigenomic approach to therapy for tamoxifen-resistant breast cancer

Qin Feng1, Zheng Zhang1, Martin J Shea2

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Cell Research
|May 31, 2014
PubMed

Insights

Tamoxifen resistance in breast cancer can be overcome. Researchers identified WHSC1 and BRD3/4 as key regulators of estrogen receptor alpha signaling, offering new therapeutic targets for tamoxifen-resistant tumors.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Tamoxifen is a primary treatment for ERα-positive breast cancer.
  • Tamoxifen resistance is a significant clinical challenge.
  • Estrogen receptor alpha (ERα) remains crucial in tamoxifen-resistant (Tam-R) breast cancer.

Purpose of the Study:

  • To identify novel regulators of ERα signaling in Tam-R breast cancer.
  • To investigate the role of histone methyl modifiers in ERα signaling.
  • To evaluate therapeutic potential of targeting identified regulators.

Main Methods:

  • Conducted a small-scale siRNA screen targeting histone methyl modifiers.
  • Investigated the recruitment of WHSC1 to the ERα gene by BRD3/4.
  • Utilized the BET protein inhibitor JQ1 in cell culture and a xenograft mouse model.
  • Assessed combination therapy with JQ1 and fulvestrant.

Main Results:

  • Identified WHSC1, a histone H3K36 methyltransferase, as a positive regulator of ERα signaling.
  • Demonstrated that BRD3/4 recruits WHSC1 to the ERα gene, enhancing its expression.
  • JQ1 suppressed ERα signaling and Tam-R breast cancer cell growth in vitro.
  • JQ1 showed in vivo anti-cancer activity and enhanced efficacy with fulvestrant in a Tam-R xenograft model.

Conclusions:

  • Epigenomic proteins BRD3/4 and WHSC1 are essential for ERα signaling in breast cancer.
  • These proteins represent novel therapeutic targets for Tam-R breast cancer.
  • Targeting BRD3/4 and WHSC1 offers a promising strategy for overcoming tamoxifen resistance.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

6.5K
Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module10:39

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

12.4K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.0K
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
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
2.6K
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