Related Experiment Video

Updated: Aug 11, 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

An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program

A S Doane1, M Danso, P Lal

  • 1Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Oncogene
|February 24, 2006
PubMed

Insights

Researchers discovered a unique subset of estrogen receptor-negative, progesterone receptor-negative breast cancer. This subtype shows hormonal regulation and responds to androgen, suggesting new therapeutic targets for this aggressive cancer.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Estrogen receptor-negative, progesterone receptor-negative (ER(-)/PR(-)) breast cancer (BC) lacks targeted therapies.
  • Tumor heterogeneity in ER(-)/PR(-) BC suggests underlying molecular subtypes.
  • Understanding the biology of these subtypes is crucial for developing new treatments.

Purpose of the Study:

  • To identify distinct molecular subsets within ER(-)/PR(-) breast cancer.
  • To gain insights into the biology of these subsets.
  • To identify potential novel therapeutic targets for ER(-)/PR(-) BC.

Main Methods:

  • Genome-wide expression analysis of 99 primary breast cancer samples and 8 BC cell lines.
  • Development of a classification model based on gene expression signatures.
  • Validation in an independent human BC dataset and cell line models.

Main Results:

  • A subset of ER(-)/PR(-) tumors exhibited paradoxical expression of estrogen-responsive genes.
  • Key differentially expressed genes included SPDEF, FOXA1, XBP1, and AR.
  • An identified cell line (MDA-MB-453) showed androgen-dependent proliferation, independent of ER, mirroring the tumor subset's signature.

Conclusions:

  • A distinct molecular subtype of ER(-)/PR(-) breast cancer is characterized by a hormonally regulated transcriptional program.
  • This subtype exhibits responsiveness to androgen.
  • Targeting the androgen signaling pathway presents a potential therapeutic strategy for this specific breast cancer subset.

More Related Videos

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:
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...
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 specific...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
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...