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Updated: Aug 18, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Selenium disrupts estrogen signaling by altering estrogen receptor expression and ligand binding in human breast
Soo Ok Lee1, Nagalakshmi Nadiminty, Xiu Xian Wu
1Department of Medicine, Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, NY 14263, USA.
Abstract:
Cancer prevention studies suggest that selenium is effective in reducing the incidence of cancers including prostate, colon, and lung cancers. Previous reports showed that selenium inhibits premalignant human breast MCF-10AT1 and MCF10AT3B cell growth in vitro and reduces mammary tumor incidence after exposure to carcinogens in tumor models. Because estrogen is critical to the development and differentiation of estrogen target tissues, including the breast, the present study was designed to examine the effect of selenium on estrogen receptor (ER) expression and activation using methylseleninic acid (MSA), an active form of selenium in vitro. Selenium decreased the levels of expression of ERalpha mRNA and protein and reduced the binding of labeled estradiol to estrogen receptor in MCF-7 cells. Selenium inhibited the trans-activating activity of estrogen receptor in MCF-7 cells expressing functional estrogen receptor using a luciferase reporter construct linked to estrogen responsive element. Selenium decreased the binding of estrogen receptor to the estrogen responsive element site using an electrophoretic mobility gel shift assay. Selenium suppressed estrogen induction of the endogenous target gene c-myc. In contrast to the effect on ERalpha in MCF-7 cells, selenium increased ERbeta mRNA expression in MDA-MB231 human breast cancer cells. Thus, differential regulation of ERalpha and ERbeta in breast cancer cells may represent a novel mechanism of selenium action and provide a rationale for selenium breast cancer prevention trial.
Insights
Selenium may prevent cancer by affecting estrogen receptors. This study shows selenium impacts estrogen receptor alpha and beta expression and activity in breast cancer cells, suggesting a new mechanism for cancer prevention.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Selenium is linked to reduced cancer incidence, particularly prostate, colon, and lung cancers.
- Previous research indicates selenium inhibits breast cell growth and mammary tumor development.
- Estrogen is crucial for breast tissue development, making its interaction with selenium significant.
Purpose of the Study:
- To investigate the effect of selenium on estrogen receptor (ER) expression and activation in breast cancer cells.
- To utilize methylseleninic acid (MSA), an active selenium form, for in vitro studies.
- To explore potential novel mechanisms of selenium's cancer-preventive action.
Main Methods:
- Assessed ERalpha mRNA and protein levels after selenium treatment in MCF-7 cells.
- Measured estradiol binding to ER in MCF-7 cells.
- Evaluated ER trans-activating activity using a luciferase reporter assay.
- Utilized electrophoretic mobility gel shift assay to study ER binding to DNA.
- Examined ERbeta mRNA expression in MDA-MB231 cells.
Main Results:
- Selenium decreased ERalpha mRNA and protein expression in MCF-7 cells.
- Selenium reduced estradiol binding to ERalpha and inhibited its DNA binding and trans-activating activity.
- Selenium suppressed estrogen-induced c-myc gene expression.
- In contrast, selenium increased ERbeta mRNA expression in MDA-MB231 cells.
Conclusions:
- Selenium differentially regulates ERalpha and ERbeta in distinct breast cancer cell lines.
- These findings suggest a novel mechanism for selenium's cancer-preventive effects.
- The study provides a rationale for further investigation in selenium breast cancer prevention trials.
