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Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion
Published on: July 6, 2022
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.
Abstract:
Oesophageal adenocarcinoma is a rapidly increasing problem in which treatment options are limited. Previous studies have shown that oesophageal adenocarcinoma cells and tissues express oestrogen receptors (ERs) and show growth suppression and apoptosis in response to ER modulator agents such as tamoxifen. ERs are known to be expressed in a number of isoforms that act together to regulate cell growth and cell death. In this study, we used western blotting to profile the expression of ERα and ERβ isoforms, and expression of the oncologically related molecules p53, HER2, and EGFR, in a panel of oesophageal adenocarcinoma cell lines. The cytotoxicity of tamoxifen in the cell lines was determined with Annexin V-FITC flow cytometry, and correlations between cytotoxicity and receptor expression were assessed using Spearman's rank-order correlation. Oesophageal adenocarcinoma cell lines showed varying cytotoxicity in response to tamoxifen. The ER species ERα90, ERα50, and ERα46, as well as p53, were positively associated with a cytotoxic response. Conversely, ERα74, ERα70, and ERβ54 were associated with a lack of cytotoxic response. The ER species detected in oesophageal adenocarcinoma cells may work together to confer sensitivity to ER modulators in this disease, which could open up a new avenue for therapy in selected patients.
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.
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