Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling

Interleukin-6 (IL-6) is a multifunctional cytokine that plays important rol es in the immune system, hematopoiesis, and acute phase reactions. Estrogen s have significant roles in a variety of biological events, such as the dev elopment and maintenance of female reproductive organs, and bone and lipid metabolism. Previous studies demonstrated that estrogens suppress IL-6-indu ced osteoporosis and the growth of multiple myeloma cells by repressing IL- 6 and IL-6 receptor gene expression. Here we present a novel mechanism for the inhibitory effect of estrogens on IL-6 function. IL-6-induced activatio n of signal transducer and activator of transcription 3 (STAT3) activity an d STAT3-mediated gene expression were suppressed by 17 beta -estradiol (E2) in breast cancer cells. E2-mediated inhibition of STAT3 activation was rev ersed by tamoxifen, an estrogen receptor (ER) antagonist. We provide eviden ce that the inhibitory action of ER on STAT3 activity was due to direct phy sical interactions between STAT3 and ER which represents a novel form of cr oss-talk between STAT3 and ER signaling pathways. (C) 2000 Federation of Eu ropean Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.