Oestrogen Receptor Isoforms May Represent a Therapeutic Target in Oesophageal Adenocarcinoma

Steven L Due1,2, David I Watson1,2, Isabell Bastian2

  • 1Department of Surgery, Flinders Medical Centre, Bedford Park, SA 5042, Australia.

Cancers
|April 23, 2022
PubMed

Insights

Oesophageal adenocarcinoma cells show varying responses to tamoxifen. Specific oestrogen receptor (ER) isoforms and p53 expression correlate with tamoxifen

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Oesophageal adenocarcinoma (EAC) is a growing concern with limited treatment options.
  • Oesophageal adenocarcinoma cells express oestrogen receptors (ERs), suggesting potential therapeutic targets.
  • ER modulators like tamoxifen can induce growth suppression and apoptosis in EAC cells.

Purpose of the Study:

  • To investigate the expression of ERα and ERβ isoforms in EAC cell lines.
  • To assess the cytotoxic effects of tamoxifen on EAC cell lines.
  • To correlate ER isoform expression with tamoxifen-induced cytotoxicity.

Main Methods:

  • Western blotting was used to profile ERα and ERβ isoforms, p53, HER2, and EGFR expression.
  • Cytotoxicity was determined using Annexin V-FITC flow cytometry.
  • Spearman's rank-order correlation was employed to assess relationships between receptor expression and cytotoxicity.

Main Results:

  • EAC cell lines exhibited differential sensitivity to tamoxifen.
  • ERα90, ERα50, ERα46, and p53 expression were positively associated with tamoxifen-induced cytotoxicity.
  • ERα74, ERα70, and ERβ54 expression correlated with resistance to tamoxifen's cytotoxic effects.

Conclusions:

  • Specific ER isoforms and p53 play a role in regulating tamoxifen sensitivity in EAC.
  • Combinatorial expression of ER isoforms may determine the response to ER modulators.
  • This finding suggests a potential new therapeutic strategy for selected EAC patients.

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:
1.7K
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...
7.0K
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:
2.9K
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...
7.9K
Dose-Response Relationship: Selectivity and Specificity01:25

Dose-Response Relationship: Selectivity and Specificity

Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and...
8.5K
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
2.2K