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Selenium disrupts estrogen signaling by altering estrogen receptor expression and ligand binding in human breast cancer cells.
Cancer Res. 2005 Apr 15; 65(8):3487-92.CR

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.

Authors+Show Affiliations

Department of Medicine, Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, NY 14263, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15833885

Citation

Lee, Soo Ok, et al. "Selenium Disrupts Estrogen Signaling By Altering Estrogen Receptor Expression and Ligand Binding in Human Breast Cancer Cells." Cancer Research, vol. 65, no. 8, 2005, pp. 3487-92.
Lee SO, Nadiminty N, Wu XX, et al. Selenium disrupts estrogen signaling by altering estrogen receptor expression and ligand binding in human breast cancer cells. Cancer Res. 2005;65(8):3487-92.
Lee, S. O., Nadiminty, N., Wu, X. X., Lou, W., Dong, Y., Ip, C., Onate, S. A., & Gao, A. C. (2005). Selenium disrupts estrogen signaling by altering estrogen receptor expression and ligand binding in human breast cancer cells. Cancer Research, 65(8), 3487-92.
Lee SO, et al. Selenium Disrupts Estrogen Signaling By Altering Estrogen Receptor Expression and Ligand Binding in Human Breast Cancer Cells. Cancer Res. 2005 Apr 15;65(8):3487-92. PubMed PMID: 15833885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selenium disrupts estrogen signaling by altering estrogen receptor expression and ligand binding in human breast cancer cells. AU - Lee,Soo Ok, AU - Nadiminty,Nagalakshmi, AU - Wu,Xiu Xian, AU - Lou,Wei, AU - Dong,Yan, AU - Ip,Clement, AU - Onate,Sergio A, AU - Gao,Allen C, PY - 2005/4/19/pubmed PY - 2005/6/4/medline PY - 2005/4/19/entrez SP - 3487 EP - 92 JF - Cancer research JO - Cancer Res VL - 65 IS - 8 N2 - 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15833885/Selenium_disrupts_estrogen_signaling_by_altering_estrogen_receptor_expression_and_ligand_binding_in_human_breast_cancer_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15833885 DB - PRIME DP - Unbound Medicine ER -