Related Experiment Video

Updated: Jun 22, 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

Signaling-dependent nuclear export of estradiol receptor controls cell cycle progression in breast cancer cells

Gabriella Castoria1, Antimo Migliaccio, Ferdinando Auricchio

  • 1Department of General Pathology, II University of Naples, Napoli, Italy. gabriella.castoria@unina2.it

Molecular and Cellular Endocrinology
|June 25, 2009
PubMed

Insights

Estradiol receptor nuclear export drives breast cancer progression and resistance to hormonal therapies. A novel peptide that mimics the estradiol receptor nuclear export sequence traps the receptor in the nucleus, blocking cancer cell growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Estradiol receptor is crucial in breast cancer, with therapies targeting its function.
  • Hormonal therapy resistance and metastasis remain significant challenges in breast cancer treatment.
  • Mislocalization of proteins, including estradiol receptor nuclear exclusion, is implicated in cancer development and therapy resistance.

Purpose of the Study:

  • To investigate the role of estradiol receptor intracellular localization in breast cancer progression and hormonal therapy resistance.
  • To identify compounds that can correct estradiol receptor mislocalization for novel anticancer drug discovery.
  • To analyze estradiol receptor nuclear export pathways and their impact on cell cycle progression.

Main Methods:

  • Dissection of estradiol receptor nuclear export in breast cancer cells.
  • Investigation of the dependence of nuclear export on PI3-K signaling.
  • Development and testing of a peptide mimicking the estradiol receptor nuclear export sequence.

Main Results:

  • Estradiol receptor nuclear exclusion is linked to breast cancer tumorigenesis and therapy resistance.
  • Estradiol receptor nuclear export significantly impacts cell cycle progression.
  • A specific peptide successfully trapped estradiol receptor in the nucleus and inhibited cancer cell proliferation.

Conclusions:

  • Targeting estradiol receptor intracellular localization offers a promising strategy for overcoming hormonal therapy resistance.
  • Modulating estradiol receptor nuclear export with specific peptides can be a viable approach for developing new breast cancer treatments.
  • Understanding the mechanisms of estradiol receptor mislocalization is key to improving breast cancer patient outcomes.

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

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Related Concept Videos

Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
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...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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.
Chemical Signaling in the Endocrine System01:08

Chemical Signaling in the Endocrine System

A signaling cascade is a series of events that facilitates the transmission of information within or between cells, culminating in a targeted response in the recipient cell. As chemical messengers, hormones are pivotal in initiating and modulating these intricate signaling cascades based on their solubility.
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...