Cross-talk between bone morphogenic proteins and estrogen receptor signaling.
Bone morphogenic proteins (BMPs) play central roles in differentiation, development, and physiological tissue remodeling. Estrogens have key roles in a variety of biological events, such as the development and maintenance of numerous target tissues. Previous studies demonstrated that estrogens suppress BMP functions by repressing BMP gene expression. Here we present a novel mechanism for the inhibitory effect of estrogens on BMP function. BMP-2-induced activation of Sma and Mad (mothers against decapentaplegic)-related protein (Smad) activity and BMP-2-mediated gene expression were suppressed by 17beta-E2 in breast cancer cells and mesangial cells. E2-mediated inhibition of Smad activation was reversed by tamoxifen, an ER antagonist. We provide evidence that the inhibitory action of ER on Smad activity was due to direct physical interactions between Smads and ER, which represents a novel mechanism for the cross-talk between BMP and ER signaling pathways.
Yamamoto
Tetsuya
T
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Saatcioglu
Fahri
F
Matsuda
Tadashi
T
D015152:Blotting, Northern; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008156:Luciferases / Q000235:genetics; D011233:Precipitin Tests; D020239:Receptor Cross-Talk / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D007202:Indicators and Reagents; D011960:Receptors, Estrogen; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D008156:Luciferases