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Steroid receptor coactivator

Chantal Beatrice Magne Nde, Gloria Casas Gimeno, Maria Docanto, Kevin C Knower, Morag J Young, Jakob Buehn, Edris Sayed, Colin D Clyne
Activation of oestrogen receptor α (ERα) stimulates cell division and tumour growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homologue of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator...
March 16, 2018: Journal of Molecular Biology
Chen Bian, Yan Huang, Haitao Zhu, Yangang Zhao, Jikai Zhao, Jiqiang Zhang
Steroids have been demonstrated to play profound roles in the regulation of hippocampal function by acting on their receptors, which need coactivators for their transcriptional activities. Previous studies have shown that steroid receptor coactivator-1 (SRC-1) is the predominant coactivator in the hippocampus, but its exact role and the underlying mechanisms remain unclear. In this study, we constructed SRC-1 RNA interference lentiviruses, injected them into the hippocampus of male mice, and then examined the changes in the expression of selected synaptic proteins, CA1 synapse density, postsynaptic density (PSD) thickness, and in vivo long-term potentiation (LTP)...
March 7, 2018: Neuroscience
Misa Hayashi, Kumi Futawaka, Midori Matsushita, Mayuko Hatai, Noriko Yoshikawa, Kazuki Nakamura, Tetsuya Tagami, Kenji Moriyama
Cigarette smoke contains over 4800 compounds, including at least 200 toxicants or endocrine disruptors. Currently, effects of cigarette smoke on thyroid hormone (TH) levels remains to be clarified. Here, we demonstrate that cigarette smoke extract (CSE) possesses thyroid hormone properties and acts synergistically as a partial agonist for thyroid hormone receptors (TRs) in the presence of TH. In transient gene expression experiments, CSE stimulated transcriptional activity with TH in a dose-dependent manner...
2018: Biological & Pharmaceutical Bulletin
Jikai Zhao, Chen Bian, Mengying Liu, Yangang Zhao, Tao Sun, Fangzhou Xing, Jiqiang Zhang
Hippocampal synaptic plasticity is the basis of spatial memory and cognition and is strongly regulated by both testicular androgens (testosterone, T) and hippocampal estrogens (17β-estradiol, E2) converted from T by aromatase, which is inhibited by letrozole (LET), but the contribution of each pathway to spatial memory and the associated mechanisms are unclear. In this study, we first used orchiectomy (ORX) and LET injection to investigate the effects of T and hippocampal E2 on spatial memory and hippocampal synaptic plasticity...
February 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
Bharti Jaiswal, Ashish Gupta
Nuclear receptors are transcription factors that binds to specific DNA sequences known as hormone response elements located upstream of their target genes. Transcriptional activity of NRs can be modulated by binding of the compatible ligand and transient interaction with cellular coregulators functioning either as coactivators or as corepressors. Many coactivator proteins possess intrinsic histone acetyl transferase (HAT) activity that catalyzes the acetylation of specific lysine residues in histone tails and loosens the histone-DNA interaction thereby facilitating access of transcriptional factors to the regulatory sequences of the DNA...
February 6, 2018: Endocrinology
Alacoque L Browne, Sara Charmsaz, Damir Varešlija, Ailis Fagan, Nicola Cosgrove, Sinéad Cocchiglia, Siobhan Purcell, Elspeth Ward, Fiona Bane, Lance Hudson, Arnold D Hill, Jason S Carroll, Aisling M Redmond, Leonie S Young
Steroid receptor coactivator 1 (SRC-1) interacts with nuclear receptors and other transcription factors (TFs) to initiate transcriptional networks and regulate downstream genes which enable the cancer cell to evade therapy and metastasise. Here we took a top-down discovery approach to map out the SRC-1 transcriptional network in endocrine resistant breast cancer. First, rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) was employed to uncover new SRC-1 TF partners. Next, RNA sequencing (RNAseq) was undertaken to investigate SRC-1 TF target genes...
January 25, 2018: Oncogene
Tianjiao Wang, Bowen Liu, Yanan Guan, Miaomiao Gong, Weiying Zhang, Jinjin Pan, Yanan Liu, Rui Liang, Yuhui Yuan, Lihong Ye
BACKGROUND: Background: Bisphenol A (BPA) is an estrogen-like chemical widely contained in daily supplies. There is evidence that environmental exposure to BPA could contribute to the development of hormone-related cancers. As is reported in numerous studies, melatonin, an endogenous hormone secreted by the pineal gland, could markedly inhibit estrogen-induced proliferation of breast cancer (BC) cells. In this study, we intended to reveal the effects of melatonin on BPA-induced proliferation of estrogen receptor-positive BC cells...
January 13, 2018: Thoracic Cancer
Thomas E Speltz, Jeanne M Danes, Joshua D Stender, Jonna Frasor, Terry W Moore
We and others have proposed that coactivator binding inhibitors, which block the interaction of estrogen receptor and steroid receptor coactivators, may represent a potential class of new breast cancer therapeutics. The development of coactivator binding inhibitors has been limited, however, because many of the current molecules which are active in in vitro and biochemical assays are not active in cell-based assays. Our goal in this work was to prepare a coactivator binding inhibitor active in cellular models of breast cancer...
January 8, 2018: ACS Chemical Biology
Subha Sen, Fei Wang, Jing Zhang, Zhiheng He, Jian Ma, Yousang Gwack, Jianming Xu, Zuoming Sun
Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the lineage decision for the development of Th17 versus induced T-regulatory (iTreg) cells. We demonstrate that SRC1 functions as a critical coactivator for RORγt in vivo to promote the functional dominance of RORγt over Foxp3 and thus establishing an unopposed Th17 differentiation program...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
Zhilin Li, Aijun Yang, Xiaolong Yin, Shiwu Dong, Fei Luo, Ce Dou, Xu Lan, Zhao Xie, Tianyong Hou, Jianzhong Xu, Junchao Xing
Tissue-engineered constructs (TECs) hold great promise for treating large bone defects. Incorporated mesenchymal stem cells (MSCs) can facilitate the vascularization of TECs. Nevertheless, the underlying mechanism remains ambiguous. Here we analyzed the roles of C-X-C chemokine receptor 2 (CXCR2) and its downstream signal pathways in MSC-induced endothelial progenitor cell (EPC) migration. Transwell assays and immunofluorescence staining were performed for cell migration analysis in vitro and in vivo, respectively...
January 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Guillaume E Courtoy, Jacques Donnez, Etienne Marbaix, Matilde Barreira, Mathieu Luyckx, Marie-Madeleine Dolmans
OBJECTIVE: To investigate whether ulipristal acetate (UPA) treatment modifies the expression of progesterone receptor (PR), its nuclear cofactors steroid receptor coactivator-1 (SRC1) and nuclear corepressor-1 (NCoR1), prosurvival factor B-cell lymphoma 2 (Bcl-2), and Akt in uterine myomas. PATIENTS: Prospective study of 59 women with symptomatic myomas undergoing myomectomy. Forty-two patients were treated preoperatively with UPA; the remaining 17 were not and they served as controls...
December 11, 2017: Gynecologic and Obstetric Investigation
Wei Xiong, Changkun Huang, Huanghao Deng, Chengzhu Jian, Cong Zen, Kun Ye, Zhaohui Zhong, Xiaokun Zhao, Liang Zhu
Steroid receptor co-activator3 (SRC3) has been known to severe as an androgen receptor (AR) coactivator and is involved in the prostate cancer progression. Non-coding RNA (ncRNA) plays an important role in the cancer progression. However, the mechanism underlying the relationship between ncRNA and AR coactivators is still unclear. Here, we found a ncRNA, Nuclear Enriched Abundant Transcript 1 (NEAT1), was able to interact with SRC3 in the prostate cancer cell lines. NEAT1 can upregulate the AKT phosphorylation via a SRC3/IGF1R pathway...
January 2018: International Journal of Biochemistry & Cell Biology
Yunu Jung, Jinbong Park, Hye-Lin Kim, Dong-Hyun Youn, JongWook Kang, Seona Lim, Mi-Young Jeong, Gautam Sethi, Sung-Joo Park, Kwang Seok Ahn, Jae-Young Um
Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA...
October 20, 2017: Oncotarget
Jia-Sin Yang, Chiao-Wen Lin, Yi-Hsien Hsieh, Ming-Hsien Chien, Chun-Yi Chuang, Shun-Fa Yang
Oral cancer is a solid malignant tumor that is prone to occur following hypoxia. There are no clear studies showing a link between hypoxia and oral carcinogenesis. Carbonic anhydrase IX (CAIX), which is a hypoxia-induced transmembrane protein, is highly expressed in various types of human cancer. However, the effects of CAIX on the metastasis of human oral cancer cells and the underlying molecular mechanisms have not been clarified. In this study, we observed that CAIX overexpression increased the migratory and invasive abilities of SCC-9 and SAS cells...
October 10, 2017: Oncotarget
Kalliopi Azariadis, Fotini Kiagiadaki, Vasiliki Pelekanou, Vasiliki Bempi, Kostas Alexakis, Marilena Kampa, Andreas Tsapis, Elias Castanas, George Notas
BACKGROUND/AIMS: Reports regarding the role of androgen in breast cancer (BC) are conflicting. Some studies suggest that androgen could lead to undesirable responses in the presence of certain BC tumor characteristics. We have shown that androgen induces C-X-C motif chemokine 12 (CXCL12) in BC cell lines. Our aim was to identify the mechanisms regulating the phenotypic effects of androgen-induced CXCL12 on Androgen Receptor (AR) positive BC cell lines. METHODS: We analyzed the expression of CXCL12 and its receptors with qPCR and ELISA and the role of Nuclear Receptor Coactivator 1 (NCOA1) in this effect...
November 3, 2017: Cellular Physiology and Biochemistry
Ji Ho Suh, Li Lai, Deokhwa Nam, Jong Kim, Juyeon Jo, George E Taffet, Eunah Kim, Jason T Kaelber, Hyun-Kyoung Lee, Mark L Entman, John P Cooke, Erin L Reineke
Pressure overload-induced cardiac stress induces left ventricular hypertrophy driven by increased cardiomyocyte mass. The increased energetic demand and cardiomyocyte size during hypertrophy necessitate increased fuel and oxygen delivery and stimulate angiogenesis in the left ventricular wall. We have previously shown that the transcriptional regulator steroid receptor coactivator-2 (SRC-2) controls activation of several key cardiac transcription factors and that SRC-2 loss results in extensive cardiac transcriptional remodeling...
November 10, 2017: Journal of Biological Chemistry
Xiaohui Zhao, Dayu Zhou, Yunen Liu, Chun Li, Xiaoguang Zhao, Ying Li, Wei Li
Prostate cancer is one of the most common types of malignant tumor of men worldwide and the incidence and mortality rate is gradually increasing. At present, the molecular mechanisms of growth and migration in human prostate cancer have not been completely elucidated. Studies have demonstrated that Ganoderma lucidum polysaccharides (GLP) can inhibit cancer. Therefore the present study investigated the effect and molecular mechanism of GLP on cell growth and migration of LNCaP human prostate cancer cells. LNCaP cells were transfected with either a protein arginine methyltransferase 6 (PRMT6) overexpression plasmid or PRMT6 small interfering (si)RNA...
January 2018: Molecular Medicine Reports
Yuichiro Kanno, Yuki Kure, Saori Kobayashi, Mariko Mizuno, Yumi Tsuchiya, Naoya Yamashita, Kiyomitsu Nemoto, Yoshio Inouye
The constitutive active/androstane receptor (CAR) is a nuclear receptor that acts as a transcription factor for a variety of genes, including genes encoding xenobiotic, steroid and drug-metabolizing enzymes and transporters. Transactivation of a target gene by a transcription factor is generally mediated through the concerted and stepwise recruitment of various proteins termed co-regulators, including coactivators and corepressors. In this study, tripartite motif containing 24 (TRIM24; also known as transcriptional intermediary factor 1 alpha) was found to interact with the CAR...
November 3, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Hongchao Cao, Shengjie Zhang, Shifang Shan, Chao Sun, Yan Li, Hui Wang, Shuxian Yu, Yi Liu, Feifan Guo, Qiwei Zhai, Yu-Cheng Wang, Jingjing Jiang, Hui Wang, Jun Yan, Wei Liu, Hao Ying
Nuclear receptors (NRs) regulate gene transcription by recruiting coregulators, involved in chromatin remodeling and assembly of the basal transcription machinery. The NR-associated protein ligand-dependent corepressor (LCoR) has previously been shown to suppress hepatic lipogenesis by decreasing the binding of steroid receptor coactivators to thyroid hormone receptor. However, the role of LCoR in adipogenesis has not been established. Here, we show that LCoR expression is reduced in the early stage of adipogenesis in vitro LCoR overexpression inhibited 3T3-L1 adipocyte differentiation, whereas LCoR knockdown promoted it...
November 17, 2017: Journal of Biological Chemistry
Lan Shen, Fang Zhang, Ruimin Huang, Jun Yan, Bing Shen
Urinary bladder cancer (UBC) is one of the most common urological cancer types. Muscle invasive bladder cancer possesses high propensity for metastasis with poor prognosis. Honokiol is a lignan isolated from Magnolia officinalis with high bioavailability and potent anticancer effects. The results of the present study demonstrated that honokiol significantly inhibited UBC cell migration and invasion in a dose-dependent manner compared with the vehicle-treated control group. In addition, honokiol treatment suppressed epithelial-mesenchymal transition by induction of E-cadherin and repression of N-cadherin...
October 2017: Oncology Letters
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