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Cross‐talk between signal transducer and activator of transcription 3 and estrogen receptor signaling
Author(s) -
Yamamoto Tetsuya,
Matsuda Tadashi,
Junicho Akira,
Kishi Hiroyuki,
Saatcioglu Fahri,
Muraguchi Atsushi
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02296-1
Subject(s) - stat3 , stat protein , estrogen receptor , signal transduction , estrogen receptor alpha , estrogen , estrogen receptor beta , cancer research , microbiology and biotechnology , biology , tamoxifen , cytokine , receptor , interleukin 6 , socs3 , medicine , endocrinology , chemistry , immunology , breast cancer , cancer
Interleukin‐6 (IL‐6) is a multifunctional cytokine that plays important roles in the immune system, hematopoiesis, and acute phase reactions. Estrogens have significant roles in a variety of biological events, such as the development and maintenance of female reproductive organs, and bone and lipid metabolism. Previous studies demonstrated that estrogens suppress IL‐6‐induced 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 activation of signal transducer and activator of transcription 3 (STAT3) activity and STAT3‐mediated gene expression were suppressed by 17β‐estradiol (E2) in breast cancer cells. E2‐mediated inhibition of STAT3 activation was reversed by tamoxifen, an estrogen receptor (ER) antagonist. We provide evidence that the inhibitory action of ER on STAT3 activity was due to direct physical interactions between STAT3 and ER which represents a novel form of cross‐talk between STAT3 and ER signaling pathways.