title: 17beta-Estradiol inhibits osteoprotegerin production by the estrogen receptor-alpha-positive human breast cancer cell line MCF-7.
abstract: Estrogen regulates various cytokines and growth factors in estrogen receptor (ER)-positive human breast cancer. Receptor activator of NF-kappaB ligand (RANKL) is an essential cytokine for osteoclasts, whereas osteoprotegerin (OPG) is a soluble inhibitor for RANKL. We analyzed the regulation of the RANKL/OPG system by estrogens and androgens in the ER-positive breast cancer cell line MCF-7 and the ER-negative breast cancer cell line MDA-MB-231. In MCF-7 cells, which predominantly express ER-alpha, 17beta-estradiol and testosterone dose-dependently decreased OPG mRNA levels and protein secretion by 70 and 65%, respectively (p<0.0001 by ANOVA). The inhibition of OPG production by 17beta-estradiol and testosterone was specifically prevented by the pure anti-estrogen ICI 182,780, and the testosterone effect was prevented by an aromatase inhibitor. In conclusion, 17beta-estradiol suppressed OPG production by human breast cancer cell lines in a dose-dependent and specific manner, indicating that the RANKL/OPG cytokine system is an estrogen-responsive target in breast cancer.
authors.affiliation: Division of Gastroenterology and Endocrinology, Department of Medicine, Philipps-University, Marburg, Germany.
authors.forename: Tilman D
authors.initials: TD
authors.lastname: Rachner
authors.forename: Michael
authors.initials: M
authors.lastname: Schoppet
authors.forename: Ute
authors.initials: U
authors.lastname: Niebergall
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053244:Osteoprotegerin / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D053244:Osteoprotegerin; D004958:Estradiol