Oestrogen Receptor Isoforms May Represent a Therapeutic Target in Oesophageal Adenocarcinoma

SIMPLE SUMMARY: Oesophageal adenocarcinoma is a lethal malignancy with limited treatment options. Recent studies have identified oestrogen receptors (ERs) in this cancer, which could represent a new target for therapy. In this study, we used laboratory models of oesophageal adenocarcinoma to look for the presence of variant forms of ERs. We also assessed the response to treatment with a drug that acts through these ERs. We found that variant forms of ERs do exist in this malignancy and that some of the variants appear to be important in order for the cells to respond to treatment. This could be due to interactions between different ERs, or between ERs and other molecules that are known to be important in cancer growth. Our findings are encouraging in that drugs that act through ERs might be useful for patients with oesophageal adenocarcinoma in the future. 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.