title: Suppression of estrogen receptor transcriptional activity by connective tissue growth factor.
abstract: Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER) that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF) physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs.
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Jiao
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Juqiang
authors.initials: J
authors.lastname: Han
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
mesh_terms: D015153:Blotting, Western; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D011485:Protein Binding; D034622:RNA Interference / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D055513:Connective Tissue Growth Factor