Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

    1. Jan-Åke Gustafsson1,2
    1. 1Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3605 Cullen Blvd, Science and Engineering Research Center Bldg 545, Houston, Texas 77204-5056, USA
      2Department of Biosciences and Nutrition, Karolinska Institutet, Novum, S-141 57 Huddinge, Sweden
    1. Correspondence should be addressed to J-Å Gustafsson; Email: jgustafsson{at}


    Estrogen and its receptors (ERs) influence many biological processes in physiology and pathology in men and women. ERs are involved in the etiology and/or progression of cancers of the prostate, breast, uterus, ovary, colon, lung, stomach, and malignancies of the immune system. In estrogen-sensitive malignancies, ERβ usually is a tumor suppressor and ERα is an oncogene. ERβ regulates genes in several key pathways including tumor suppression (p53, PTEN); metabolism (PI3K); survival (Akt); proliferation pathways (p45Skp2, cMyc, and cyclin E); cell-cycle arresting factors (p21WAF1, cyclin-dependent kinase inhibitor 1 (CDKN1A)), p27Kip1, and cyclin-dependent kinases (CDKs); protection from reactive oxygen species, glutathione peroxidase. Because they are activated by small molecules, ERs are excellent targets for pharmaceuticals. ERα antagonists have been used for many years in the treatment of breast cancer and more recently pharmaceutical companies have produced agonists which are very selective for ERα or ERβ. ERβ agonists are being considered for preventing progression of cancer, treatment of anxiety and depression, as anti-inflammatory agents and as agents, which prevent or reduce the severity of neurodegenerative diseases.

    • Revision received 4 September 2013
    • Accepted 9 September 2013
    • Made available online as an Accepted Preprint 12 September 2013
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