Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells

Olga Sukocheva, Christopher Wee, Alfiya Ansar, Damian Hussey, David Watson

    Research output: Contribution to journalArticle

    32 Citations (Scopus)

    Abstract

    The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is that estrogen might protect against esophageal adenocarcinoma. Estrogen has previously been shown to stimulate apoptosis in esophageal squamous cancer cells. However, the effect of estrogen on esophageal adenocarcinoma cells has not been determined. We used immunoblotting analysis to determine the expression of estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki-67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen receptor modulator (SERM)-dependent effects on cell growth were determined by the CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin V/Propidium Iodide cell labeling and flow cytometry. We detected that physiological and supra-physiological concentrations of 17β-estradiol and SERM decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus cells (QhTRT, ChTRT), decreased growth was also detected in response to estrogen/SERM. The level of estrogen receptor expression in the cell lines correlated with the level of anti-growth effects induced by the receptor agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a decrease in the expression of Ki-67 and an increase in E-cadherin expression in esophageal adenocarcinoma cells. This study suggests that esophageal adenocarcinoma and Barrett's esophagus cells respond to treatment with selective estrogen receptor ligands, resulting in decreased cell growth and apoptosis. Further research to explore potential therapeutic applications is warranted.

    Original languageEnglish
    Pages (from-to)628-635
    Number of pages8
    JournalDiseases of The Esophagus
    Volume26
    Issue number6
    Early online date2013
    DOIs
    Publication statusPublished - Aug 2013

    Keywords

    • Apoptosis
    • Barrett's esophagus
    • Esophageal adenocarcinoma
    • Estrogen
    • Tamoxifen raloxifene

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