17beta-Estradiol inhibits osteoprotegerin production by the estrogen receptor-alpha-positive human breast cancer cell line MCF-7 |
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Authors: | Rachner Tilman D Schoppet Michael Niebergall Ute Hofbauer Lorenz C |
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Institution: | a Division of Gastroenterology and Endocrinology, Department of Medicine, Philipps-University, Marburg, Germany b Department of Medicine and Cardiology, Philipps-University, Marburg, Germany c Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technical University of Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany |
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Abstract: | Estrogen regulates various cytokines and growth factors in estrogen receptor (ER)-positive human breast cancer. Receptor activator of NF-κB 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-α, 17β-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 17β-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, 17β-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. |
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Keywords: | Estrogen Estrogen receptor Breast cancer Osteoprotegerin |
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