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Steroid receptor coactivator

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https://www.readbyqxmd.com/read/28631712/-the-molecular-mechanisms-and-morphological-manifestations-of-leiomyoma-reduction-induced-by-selective-progesterone-receptor-modulators
#1
T A Demura, Z V Revazova, E A Kogan, L V Adamyan
AIM: to investigate the molecular mechanisms and morphological substrate of reduced uterine leiomyoma in patients receiving the selective progesterone receptor modulator (SPRM) ulipristal acetate for 3 months, by estimating the immunohistochemical expression of the markers steroid receptor coactivator 1 (SRC-1), nuclear receptor corepressor 1 (NCoR-1), ER, PgR, Ki-67, p16, TGF-β, and VEGF in tumor tissue. SUBJECTS AND METHODS: The investigation enrolled 75 women with uterine leiomyoma, menorrhagias, and anemia...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28611094/agonist-specific-protein-interactomes-of-glucocorticoid-and-androgen-receptor-as-revealed-by-proximity-mapping
#2
Joanna K Lempiäinen, Einari A Niskanen, Kaisa-Mari Vuoti, Riikka E Lampinen, Helka Göös, Markku Varjosalo, Jorma J Palvimo
Glucocorticoid receptor (GR) and androgen receptor (AR) are steroid-inducible transcription factors (TFs). GR and AR are central regulators of various metabolic, homeostatic and differentiation processes and hence important therapeutic targets, especially in inflammation and prostate cancer, respectively. Hormone binding to these steroid receptors (SRs) leads to DNA binding and activation or repression of their target genes with the aid of interacting proteins, coregulators. However, protein interactomes of these important drug targets have remained poorly defined...
June 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28611048/targeting-src-coactivators-blocks-the-tumor-initiating-capacity-of-cancer-stem-like-cells
#3
Aarti D Rohira, Fei Yan, Lei Wang, Jin Wang, Suoling Zhou, Andrew Lu, Yang Yu, Jianming Xu, David M Lonard, Bert W O'Malley
Tumor initiating cells (TICs) represent cancer stem-like cell (CSC) subpopulations within tumors that are thought to give rise to recurrent cancer after therapy. Identifying key regulators of TIC/CSC maintenance is essential for the development of therapeutics designed to limit recurrence. The steroid receptor coactivator 3 (SRC-3) is overexpressed in a wide range of cancers, driving tumor initiation, cell proliferation and, metastasis. Here, we report that SRC-3 supports the TIC/CSC state and induces an epithelial to mesenchymal transition (EMT) by driving expression of the master EMT regulators and stem cell markers...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28610887/a-hormonal-cue-promotes-timely-follicle-cell-migration-by-modulating-transcription-profiles
#4
Lathiena Manning, Jinal Sheth, Stacey Bridges, Afsoon Saadin, Kamsi Odinammadu, Deborah Andrew, Susan Spencer, Denise Montell, Michelle Starz-Gaiano
Cell migration is essential during animal development. In the Drosophila ovary, the steroid hormone ecdysone coordinates nutrient sensing, growth, and the timing of morphogenesis events including border cell migration. To identify downstream effectors of ecdysone signaling, we profiled gene expression in wild-type follicle cells compared to cells expressing a dominant negative Ecdysone receptor or its coactivator Taiman. Of approximately 400 genes that showed differences in expression, we validated 16 candidate genes for expression in border and centripetal cells, and demonstrated that seven responded to ectopic ecdysone activation by changing their transcriptional levels...
June 10, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28589840/characterization-of-a-sea-urchin-iq-motif-containing-protein-d-as-a-coactivator-of-nuclear-receptors
#5
Mi Ae Kim, Young Chang Sohn
Nuclear receptor (NR) interacting proteins, such as coactivators and corepressors, play a crucial role in specifying the transcriptional activity of the receptor. However, little is known about the functional features of the NR coregulators in marine invertebrates. Using the yeast two-hybrid screening method, a sea urchin oocyte cDNA library was screened for proteins that interact with the ligand-binding domain of human RXRα (hRXRα) as the bait protein in the presence of 9-cis retinoic acid. Here, we describe IQ motif containing protein D (IQCD) as an RXR-interacting coactivator...
June 2017: Zoological Science
https://www.readbyqxmd.com/read/28521488/mir-137-inhibits-the-proliferation-of-human-non-small-cell-lung-cancer-cells-by-targeting-src3
#6
Ruilin Chen, Yongqing Zhang, Chengcheng Zhang, Hua Wu, Shumei Yang
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The results of the present study demonstrate that high expression of microRNA (miR)-137 and low expression of steroid receptor coactivator-3 (SRC3) had a significant negative correlation in 40 NSCLC tissue samples. In addition, cell colony formation and proliferation was significantly reduced in miR-137-transfected A549 and NCI-H838 cells compared with scramble-transfected NSCLC cell lines. miR-137 was identified to induce G1/S cell cycle arrest and dysregulate the mRNA expression of cell cycle-associated proteins (proliferating cell nuclear antigen, cyclin E, cyclin A1, cyclin A2 and p21) in NSCLC cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521442/mrna-expression-of-steroidogenic-enzymes-steroid-hormone-receptors-and-their-coregulators-in-gastric-cancer
#7
Bartosz Adam Frycz, Dawid Murawa, Maciej Borejsza-Wysocki, Mateusz Wichtowski, Arkadiusz Spychała, Ryszard Marciniak, Paweł Murawa, Michał Drews, Paweł Piotr Jagodziński
Epidemiological and experimental findings suggest that the development of gastric cancer (GC) is regulated by steroid hormones. In postmenopausal women and older men, the majority of steroid hormones are produced locally in peripheral tissue through the enzymatic conversion of steroid precursors. Therefore, using reverse transcription-quantitative polymerase chain reaction analysis, the mRNA expression of genes encoding steroidogenic enzymes, including steroid sulfatase (STS), hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1), 17β-hydroxysteroid dehydrogenase type 7 and aromatase (CYP19A1), was investigated in primary tumoral and adjacent healthy gastric mucosa from 60 patients with GC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28468300/nobiletin-inhibits-angiogenesis-by-regulating-src-fak-stat3-mediated-signaling-through-pxn-in-er%C3%A2-%C2%BA-breast-cancer-cells
#8
Nipin Sp, Dong Young Kang, Youn Hee Joung, Jong Hwan Park, Wan Seop Kim, Hak Kyo Lee, Ki-Duk Song, Yeong-Min Park, Young Mok Yang
Tumor angiogenesis is one of the major hallmarks of tumor progression. Nobiletin is a natural flavonoid isolated from citrus peel that has anti-angiogenic activity. Steroid receptor coactivator (Src) is an intracellular tyrosine kinase so that focal adhesion kinase (FAK) binds to Src to play a role in tumor angiogenesis. Signal transducer and activator of transcription 3 (STAT3) is a marker for tumor angiogenesis which interacts with Src. Paxillin (PXN) acts as a downstream target for both FAK and STAT3. The main goal of this study was to assess inhibition of tumor angiogenesis by nobiletin in estrogen receptor positive (ER⁺) breast cancer cells via Src, FAK, and STAT3-mediated signaling through PXN...
April 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28396297/the-co-regulators-src-1-and-smrt-are-involved-in-interleukin-6-induced-androgen-receptor-activation
#9
Qi Wang, Hui Wang, Qiang Ju, Zhen Ding, Xing Ge, Qiao-Mei Shi, Ji-Long Zhou, Xiao-Long Zhou, Jin-Peng Zhang, Mei-Rong Zhang, Hong-Min Yu, Li-Chun Xu
BACKGROUND: The androgen receptor (AR) can be stimulated by interleukin-6 (IL-6) in the absence of androgens to induce prostate cancer progression. The purpose of this study was to investigate whether the co-activator steroid receptor coactivator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) are involved in IL-6-induced AR activation. METHODS: The effects of IL-6 on LNCaP cell proliferation were monitored using real-time cell analysis (RTCA) iCELLigence system...
November 1, 2016: European Cytokine Network
https://www.readbyqxmd.com/read/28390937/steroid-receptor-coactivators-present-a-unique-opportunity-for-drug-development-in-hormone-dependent-cancers
#10
REVIEW
Aarti D Rohira, David M Lonard
Steroid receptor coactivators (SRCs) are essential regulators of nuclear hormone receptor function. SRCs coactivate transcription mediated by hormone stimulation of nuclear receptors and other transcription factors and have essential functions in human physiology and health. The SRCs are over expressed in a number of cancers such as breast, prostate, endometrial and pancreatic cancers where they promote tumor growth, invasion, metastasis and chemo-resistance. With their multiple roles in cancer, the SRCs are promising targets for the development of small molecule agents that can interfere with their function...
April 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28378812/ecr-recruits-dmi-2-and-increases-efficiency-of-dmi-2-mediated-remodelling-to-constrain-transcription-of-hormone-regulated-genes
#11
Judith Kreher, Kristina Kovač, Karim Bouazoune, Igor Mačinković, Anna Luise Ernst, Erik Engelen, Roman Pahl, Florian Finkernagel, Magdalena Murawska, Ikram Ullah, Alexander Brehm
Gene regulation by steroid hormones plays important roles in health and disease. In Drosophila, the hormone ecdysone governs transitions between key developmental stages. Ecdysone-regulated genes are bound by a heterodimer of ecdysone receptor (EcR) and Ultraspiracle. According to the bimodal switch model, steroid hormone receptors recruit corepressors in the absence of hormone and coactivators in its presence. Here we show that the nucleosome remodeller dMi-2 is recruited to ecdysone-regulated genes to limit transcription...
April 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28322350/agonist-mediated-assembly-of-the-crustacean-methyl-farnesoate-receptor
#12
Elizabeth K Medlock Kakaley, Helen Y Wang, Gerald A LeBlanc
The methyl farnesoate receptor (MfR) orchestrates aspects of reproduction and development such as male sex determination in branchiopod crustaceans. Phenotypic endpoints regulated by the receptor have been well-documented, but molecular interactions involved in receptor activation remain elusive. We hypothesized that the MfR subunits, methoprene-tolerant transcription factor (Met) and steroid receptor coactivator (SRC), would be expressed coincident with the timing of sex programming of developing oocytes by methyl farnesoate in daphnids...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288941/differential-activation-of-pregnane-x-receptor-by-carnosic-acid-carnosol-ursolic-acid-and-rosmarinic-acid
#13
Chun Ling Seow, Aik Jiang Lau
Pregnane X receptor (PXR) regulates the expression of many genes, including those involved in drug metabolism and transport, and has been linked to various diseases, including inflammatory bowel disease. In the present study, we determined whether carnosic acid and other chemicals in rosemary extract (carnosol, ursolic acid, and rosmarinic acid) are PXR activators. As assessed in dual-luciferase reporter gene assays, carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, activated human PXR (hPXR) and mouse PXR (mPXR), whereas carnosol and ursolic acid, but not carnosic acid or rosmarinic acid, activated rat PXR (rPXR)...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28286232/steroid-receptor-coactivator-1-can-regulate-osteoblastogenesis-independently-of-estrogen
#14
R J Watters, R J Hartmaier, H U Osmanbeyoglu, R M Gillihan, J M Rae, L Liao, K Chen, W Li, X Lu, S Oesterreich
Steroid receptor coactivator-1 (SRC-1), a well-studied coactivator of estrogen receptor (ER), is known to play an important and functional role in the development and maintenance of bone tissue. Previous reports suggest SRC-1 maintains bone mineral density primarily through its interaction with ER. Here we demonstrate that SRC-1 can also affect bone development independent of estrogen signaling as ovariectomized SRC-1 knockout (SRC-1 KO) mouse had decreased bone mineral density. To identify estrogen-independent SRC-1 target genes in osteoblastogenesis, we undertook an integrated analysis utilizing ChIP-Seq and mRNA microarray in transformed osteoblast-like U2OS-ERα cells...
March 7, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28286026/clonorchis-sinensis-excretory-secretory-products-promote-the-migration-and-invasion-of-cholangiocarcinoma-cells-by-activating-the-integrin-%C3%AE-4-fak-src-signaling-pathway
#15
Jhang Ho Pak, Qudsia Bashir, In Ki Kim, Sung-Jong Hong, Sejung Maeng, Young Yil Bahk, Tong-Soo Kim
Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion...
March 8, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28273073/src-2-mediated-coactivation-of-anti-tumorigenic-target-genes-suppresses-myc-induced-liver-cancer
#16
Shruthy Suresh, Deniz Durakoglugil, Xiaorong Zhou, Bokai Zhu, Sarah A Comerford, Chao Xing, Xian-Jin Xie, Brian York, Kathryn A O'Donnell
Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#17
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28053238/steroid-receptor-coactivator-3-contributes-to-host-defense-against-enteric-bacteria-by-recruiting-neutrophils-via-upregulation-of-cxcl2-expression
#18
Wenbo Chen, Xuqiang Lu, Yuan Chen, Ming Li, Pingli Mo, Zhangwei Tong, Wei Wang, Wei Wan, Guoqiang Su, Jianming Xu, Chundong Yu
Steroid receptor coactivator 3 (SRC-3) is a transcriptional coactivator that interacts with nuclear receptors and some other transcription factors to enhance their effects on target gene transcription. We reported previously that SRC-3-deficient (SRC-3(-/-)) mice are extremely susceptible to Escherichia coli-induced septic peritonitis as a result of uncontrolled inflammation and a defect in bacterial clearance. In this study, we observed significant upregulation of SRC-3 in colonic epithelial cells in response to Citrobacter rodentium infection...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28042453/design-and-synthesis-of-selective-small-molecule-inhibitors-of-coactivator-associated-arginine-methyltransferase-1-carm1
#19
H Ü Kaniskan, M S Eram, J Liu, D Smil, M L Martini, Y Shen, V Santhakumar, P J Brown, C Arrowsmith, M Vedadi, J Jin
Coactivator-associated arginine methyltransferase 1 (CARM1) is a type I protein arginine methyltransferase (PRMT) that catalyzes the conversion of arginine into monomethylarginine (MMA) and further into asymmetric dimethylarginine (ADMA). CARM1 methylates histone 3 arginines 17 and 26, as well as numerous non-histone proteins including CBP/p300, SRC-3, NCOA2, PABP1, and SAP49, while also functioning as a coactivator for various proteins that have been linked to cancer such as p53, NF-κβ, β-catenin, E2F1 and steroid hormone receptor ERα...
September 1, 2016: MedChemComm
https://www.readbyqxmd.com/read/28006821/src-1-regulates-blood-pressure-and-aortic-stiffness-in-female-mice
#20
Antentor Othrell Hinton, Yongjie Yang, Ann P Quick, Pingwen Xu, Chitra L Reddy, Xiaofeng Yan, Corey L Reynolds, Qingchun Tong, Liangru Zhu, Jianming Xu, Xander H T Wehrens, Yong Xu, Anilkumar K Reddy
Framingham Heart Study suggests that dysfunction of steroid receptor coactivator-1 may be involved in the development of hypertension. However, there is no functional evidence linking steroid receptor coactivator-1 to the regulation of blood pressure. We used immunohistochemistry to map the expression of steroid receptor coactivator-1 protein in mouse brain, especially in regions implicated in the regulation of blood pressure. Steroid receptor coactivator-1 protein was found in central amygdala, medial amygdala, supraoptic nucleus, arcuate nucleus, ventromedial, dorsomedial, paraventricular hypothalamus, and nucleus of the solitary tract...
2016: PloS One
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