title: Estrogen receptor β: switching to a new partner and escaping from estrogen.
abstract: Estrogen receptor (ER) β, the "second" ER, plays a gatekeeper role by inhibiting cell proliferation, promoting apoptosis, and impeding the progression of prostate cancer. Ironically, its presumed ligand, 17β-estradiol, promotes cancer development in experimental models. The mechanisms underlying the interplay between estrogens and ERβ in prostate cancer remain largely unclear. Research on a previously unknown tethering partner of ERβ, Krüppel-like zinc finger transcription factor 5 (KLF5), and its downstream gene target (FOXO1) helps to unlock this puzzle. 17β-Estradiol is not required to maintain the tumor-suppressive function of ERβ in the prostate, a tissue with limited estrogen availability; moreover, the presence of 17β-estradiol abrogates ERβ- and KLF5-mediated signaling and promotes cellular proliferation. Future research into ERβ will likely involve this estrogen independency and the preference for binding nonclassical DNA elements through tethering. The development of ERβ-based therapies may lead to improved drug efficacy.
authors.affiliation: Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati Medical Center, Kettering Complex, Room 128, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH 45267, USA.
authors.forename: Yuet-Kin
authors.initials: YK
authors.lastname: Leung
authors.forename: Shuk-Mei
authors.initials: SM
authors.lastname: Ho
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008957:Models, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D004958:Estradiol