title: Estrogen receptor beta as target for colorectal cancer prevention.
abstract: Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive approaches are not sufficient. However, a role for estrogen has been demonstrated in multiple epidemiologic studies, which may benefit CRC prevention. A large body of evidence from preclinical studies indicates that expression of the estrogen receptor beta (ERβ/ESR2) demonstrates an inverse relationship with the presence of colorectal polyps and stage of tumors, and can mediate a protective response. Natural compounds, including phytoestrogens, or synthetic ERβ selective agonists, can activate or upregulate ERβ in the colon and promote apoptosis in preclinical models and in clinical experience. Importantly, this activity has been associated with a reduction in polyp formation and, in rodent models of CRC, has been shown to lower incidence of colon adenocarcinoma. Collectively, these findings indicate that targeted activation of ERβ may represent a novel clinical approach for management of colorectal adenomatous polyps and prevention of colorectal carcinoma in patients at risk for this condition. In this review, we discuss the potential of new chemopreventive or dietary approaches based on estrogen signaling.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5056, USA; SciLifeLab, School of Biotechnology, KTH Royal Institute of Technology, 171 21 Solna, Sweden; Department of Biosciences and Nutrition, Novum, Karolinska Institutet, 141 83 Stockholm, Sweden. Electronic address: Cecilia.Williams@scilifelab.se.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: DiLeo
authors.affiliation: Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Petach Tikva 49100, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Niv
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5056, USA; Department of Biosciences and Nutrition, Novum, Karolinska Institutet, 141 83 Stockholm, Sweden.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018256:Adenomatous Polyps / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D065171:Estrogen Receptor Antagonists / Q000627:therapeutic use*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D065171:Estrogen Receptor Antagonists; D047629:Estrogen Receptor beta
keywords: Colorectal cancer; Estrogen; Estrogen receptor beta; Gene expression; Phytoestrogens; Prevention