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Attenuation of Estrogen Receptor α (ERα) Signaling by Selenium in Breast Cancer Cells via Downregulation of ERα Gene Expression

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Summary

Numerous studies have shown that selenium provides beneficial effects as a cancer chemoprevention agent. Although long-term intervention trials failed to confirm selenium protection against breast cancer in humans because of insufficient cases, the evidence of effective selenium chemoprevention in animal mammary tumor models or human breast cancer cells is substantial and convincing. The present study demonstrates that the selenium compound methylseleninic acid (MSA) inhibits estrogen receptor α (ERα) signaling in ER-positive MCF-7 breast cancer cells as evidenced by decreased estradiol-dependent cell growth and gene expression. MSA diminishes estradiol induction of endogenous ER-regulated pS2 and c-myc genes as well as the expression of an ER-regulated reporter gene. A major mode of MSA action on ER signaling is through a downregulation of ERα gene expression that precedes a decrease in ERα protein level. This study provides a mechanism driven rationale for using selenium as a chemopreventive agent for women at high risk for developing breast cancer or as a therapeutic strategy for ER-positive breast cancer.

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Authors and Affiliations

  1. Department of Biochemistry & Cancer Biology, Medical College of Ohio, Toledo, OH, USA

    Yatrik M. Shah, Aparna Kaul & Brian G. Rowan

  2. Department of Cancer Chemoprevention, Roswell Park Cancer Institute, Buffalo, New York, USA

    Yan Dong & Clement Ip

  3. Department of Structural & Cellular Biology, Tulane University School of Medicine, 1430 Tulane Avenue, Box SL49, 70112, New Orleans, LA

    Brian G. Rowan

Authors
  1. Yatrik M. Shah
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  2. Aparna Kaul
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  3. Yan Dong
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  4. Clement Ip
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  5. Brian G. Rowan
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Correspondence to Brian G. Rowan.

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Shah, Y.M., Kaul, A., Dong, Y. et al. Attenuation of Estrogen Receptor α (ERα) Signaling by Selenium in Breast Cancer Cells via Downregulation of ERα Gene Expression. Breast Cancer Res Treat 92, 239–250 (2005). https://doi.org/10.1007/s10549-005-3203-5

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