title: Estrogen receptors in breast carcinogenesis and endocrine therapy.
abstract: Excessive exposure to estrogen has long been associated with an increased risk for developing breast cancer and anti-estrogen therapy is the gold standard of care in the treatment of estrogen receptor (ER) α-positive breast cancers. However, there are several mysteries concerning both anti-estrogen, tamoxifen, and estrogen. The most important of these are: (1) some ERα-positive breast cancers do not respond to tamoxifen; (2) some ERα-negative breast cancers do respond to tamoxifen; (3) initial or acquired resistance to tamoxifen occurs with recurrent tumors; (4) estrogen can cause marked tumor regression in long-term tamoxifen-resistant ERα-positive breast cancer. These mysteries indicate that we do not know enough about estrogen signaling to understand the effects of targeting these receptors in cancer. The discovery of ERβ, the second estrogen receptor, has added another level of complexity to estrogen signaling. This review summarizes recent publications and makes an updated portrait of ERα and ERβ in breast carcinogenesis and endocrine cancer therapy.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3605 Cullen Blvd, Science & Engineering Research Center Bldg 545, Houston, Texas 77204, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3605 Cullen Blvd, Science & Engineering Research Center Bldg 545, Houston, Texas 77204, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Warner
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3605 Cullen Blvd, Science & Engineering Research Center Bldg 545, Houston, Texas 77204, USA; Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden. Electronic address: jgustafsson@uh.edu.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D013629:Tamoxifen
keywords: ERβ-selective agonist; Estrogen receptor β; Invasive ductal carcinoma; Lobular cancer; Tumor infiltrating; leukocytes