Additional Table 3 Transcription Factors (Tfs) Information Total Tfs
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Peripheral T Cells Ets-1 Maintains IL-7 Receptor Expression In
The Journal of Immunology Ets-1 Maintains IL-7 Receptor Expression in Peripheral T Cells Roland Grenningloh,*,† Tzong-Shyuan Tai,* Nicole Frahm,†,‡,1 Tomoyuki C. Hongo,‡ Adam T. Chicoine,‡ Christian Brander,†,‡,x,{ Daniel E. Kaufmann,†,‡,‖ and I-Cheng Ho*,† The expression of CD127, the IL-7–binding subunit of the IL-7 R, is tightly regulated during the development and activation of T cells and is reduced during chronic viral infection. However, the molecular mechanism regulating the dynamic expression of CD127 is still poorly understood. In this study, we report that the transcription factor Ets-1 is required for maintaining the expression of CD127 in murine peripheral T cells. Ets-1 binds to and activates the CD127 promoter, and its absence leads to reduced CD127 expression, attenuated IL-7 signaling, and impaired IL-7–dependent homeostatic proliferation of T cells. The expression of CD127 and Ets-1 is strongly correlated in human T cells. Both CD127 and Ets-1 expression are decreased in CD8+ T cells during HIV infection. In addition, HIV-associated loss of CD127 is only observed in Ets-1low effector memory and central memory but not in Ets-1high naive CD8+ T cells. Taken together, our data identify Ets-1 as a critical regulator of CD127 expression in T cells. The Journal of Immunology, 2011, 186: 969–976. nterleukin-7 signals are required for T cell development, GABPa or another Ets protein is responsible for maintaining maintaining the naive T cell pool, mounting proper primary CD127 expression in peripheral T cells is unknown. I responses, and inducing and maintaining CD4+ and CD8+ Ets-1 (E26 transformation-specific sequence) is the founding T cell memory (1–3). -
Independence of Hif1a and Androgen Signaling Pathways in Prostate Cancer
bioRxiv preprint doi: https://doi.org/10.1101/848424; this version posted November 26, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Independence of HIF1a and androgen signaling pathways in prostate cancer Maxine GB Tran1, 2*, Becky AS Bibby3†*, Lingjian Yang3, Franklin Lo1, Anne Warren1, Deepa Shukla1, Michelle Osborne1, James Hadfield1, Thomas Carroll1, Rory Stark1, Helen Scott1, Antonio Ramos-Montoya1, Charlie Massie1, Patrick Maxwell1, Catharine ML West3, 4, Ian G. Mills5,6** and David E. Neal1** 1Uro-oncology Research Group, Cancer Research UK Cambridge Institute, Cambridge, CB02 0RE, United Kingdom 2UCL division of Surgery and Interventional Science, Royal Free Hospital, Pond Street, London NW3 2QG 3Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom 4Manchester Biomedical Research Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom. 5Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, BT9 7AE, United Kingdom 6Nuffield Department of Surgical Sciences, University of Oxford, OX3 9DU, UK *These authors contributed equally to this work **These authors contributed equally to this work †Corresponding author email: Becky Bibby, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom, [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/848424; this version posted November 26, 2019. -
Harnessing Gene Expression Profiles for the Identification of Ex Vivo Drug
cancers Article Harnessing Gene Expression Profiles for the Identification of Ex Vivo Drug Response Genes in Pediatric Acute Myeloid Leukemia David G.J. Cucchi 1 , Costa Bachas 1 , Marry M. van den Heuvel-Eibrink 2,3, Susan T.C.J.M. Arentsen-Peters 3, Zinia J. Kwidama 1, Gerrit J. Schuurhuis 1, Yehuda G. Assaraf 4, Valérie de Haas 3 , Gertjan J.L. Kaspers 3,5 and Jacqueline Cloos 1,* 1 Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; [email protected] (D.G.J.C.); [email protected] (C.B.); [email protected] (Z.J.K.); [email protected] (G.J.S.) 2 Department of Pediatric Oncology/Hematology, Erasmus MC–Sophia Children’s Hospital, 3015 CN Rotterdam, The Netherlands; [email protected] 3 Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; [email protected] (S.T.C.J.M.A.-P.); [email protected] (V.d.H.); [email protected] (G.J.L.K.) 4 The Fred Wyszkowski Cancer Research, Laboratory, Department of Biology, Technion-Israel Institute of Technology, 3200003 Haifa, Israel; [email protected] 5 Emma’s Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, 1081 HV Amsterdam, The Netherlands * Correspondence: [email protected] Received: 21 April 2020; Accepted: 12 May 2020; Published: 15 May 2020 Abstract: Novel treatment strategies are of paramount importance to improve clinical outcomes in pediatric AML. Since chemotherapy is likely to remain the cornerstone of curative treatment of AML, insights in the molecular mechanisms that determine its cytotoxic effects could aid further treatment optimization. -
Ten Commandments for a Good Scientist
Unravelling the mechanism of differential biological responses induced by food-borne xeno- and phyto-estrogenic compounds Ana María Sotoca Covaleda Wageningen 2010 Thesis committee Thesis supervisors Prof. dr. ir. Ivonne M.C.M. Rietjens Professor of Toxicology Wageningen University Prof. dr. Albertinka J. Murk Personal chair at the sub-department of Toxicology Wageningen University Thesis co-supervisor Dr. ir. Jacques J.M. Vervoort Associate professor at the Laboratory of Biochemistry Wageningen University Other members Prof. dr. Michael R. Muller, Wageningen University Prof. dr. ir. Huub F.J. Savelkoul, Wageningen University Prof. dr. Everardus J. van Zoelen, Radboud University Nijmegen Dr. ir. Toine F.H. Bovee, RIKILT, Wageningen This research was conducted under the auspices of the Graduate School VLAG Unravelling the mechanism of differential biological responses induced by food-borne xeno- and phyto-estrogenic compounds Ana María Sotoca Covaleda Thesis submitted in fulfillment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Tuesday 14 September 2010 at 4 p.m. in the Aula Unravelling the mechanism of differential biological responses induced by food-borne xeno- and phyto-estrogenic compounds. Ana María Sotoca Covaleda Thesis Wageningen University, Wageningen, The Netherlands, 2010, With references, and with summary in Dutch. ISBN: 978-90-8585-707-5 “Caminante no hay camino, se hace camino al andar. Al andar se hace camino, y al volver la vista atrás se ve la senda que nunca se ha de volver a pisar” - Antonio Machado – A mi madre. -
Agonists and Knockdown of Estrogen Receptor Β Differentially Affect
Schüler-Toprak et al. BMC Cancer (2016) 16:951 DOI 10.1186/s12885-016-2973-y RESEARCH ARTICLE Open Access Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro Susanne Schüler-Toprak1*, Julia Häring1, Elisabeth C. Inwald1, Christoph Moehle2, Olaf Ortmann1 and Oliver Treeck1 Abstract Background: Estrogen receptor β (ERβ) is expressed in the majority of invasive breast cancer cases, irrespective of their subtype, including triple-negative breast cancer (TNBC). Thus, ERβ might be a potential target for therapy of this challenging cancer type. In this in vitro study, we examined the role of ERβ in invasion of two triple-negative breast cancer cell lines. Methods: MDA-MB-231 and HS578T breast cancer cells were treated with the specific ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol. Knockdown of ERβ expression was performed by means of siRNA transfection. Effects on cellular invasion were assessed in vitro by means of a modified Boyden chamber assay. Transcriptome analyses were performed using Affymetrix Human Gene 1.0 ST microarrays. Pathway and gene network analyses were performed by means of Genomatix and Ingenuity Pathway Analysis software. Results: Invasiveness of MBA-MB-231 and HS578T breast cancer cells decreased after treatment with ERβ agonists ERB-041 and WAY200070. Agonists Liquiritigenin and 3β-Adiol only reduced invasion of MDA-MB-231 cells. Knockdown of ERβ expression increased invasiveness of MDA-MB-231 cells about 3-fold. Transcriptome and pathway analyses revealed that ERβ knockdown led to activation of TGFβ signalling and induced expression of a network of genes with functions in extracellular matrix, tumor cell invasion and vitamin D3 metabolism. -
Accompanies CD8 T Cell Effector Function Global DNA Methylation
Global DNA Methylation Remodeling Accompanies CD8 T Cell Effector Function Christopher D. Scharer, Benjamin G. Barwick, Benjamin A. Youngblood, Rafi Ahmed and Jeremy M. Boss This information is current as of October 1, 2021. J Immunol 2013; 191:3419-3429; Prepublished online 16 August 2013; doi: 10.4049/jimmunol.1301395 http://www.jimmunol.org/content/191/6/3419 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130139 Material 5.DC1 References This article cites 81 articles, 25 of which you can access for free at: http://www.jimmunol.org/content/191/6/3419.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Global DNA Methylation Remodeling Accompanies CD8 T Cell Effector Function Christopher D. Scharer,* Benjamin G. Barwick,* Benjamin A. Youngblood,*,† Rafi Ahmed,*,† and Jeremy M. -
Human/Mouse/Rat HIF-1 Alpha/HIF1A Antibody
Human/Mouse/Rat HIF-1 alpha/HIF1A Antibody Monoclonal Mouse IgG1 Clone # 241809 Catalog Number: MAB1536 DESCRIPTION Species Reactivity Human/Mouse/Rat Specificity Detects human, mouse, and rat HIF-1 alpha/HIF1A. Source Monoclonal Mouse IgG1 Clone # 241809 Purification Protein A or G purified from hybridoma culture supernatant Immunogen E. coli-derived recombinant human HIF-1 alpha/HIF1A Arg575-Asn826 Accession # Q16665.1 Formulation Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. See Certificate of Analysis for details. *Small pack size (-SP) is supplied either lyophilized or as a 0.2 μm filtered solution in PBS. APPLICATIONS Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website. Recommended Sample Concentration Western Blot 1 µg/mL See Below Immunohistochemistry 5-25 µg/mL See Below Immunoprecipitation 1-3 µg/500 µg cell MCF‑7 human breast cancer cell line treated with CoCl2, see our available Western blot lysate detection antibodies Simple Western 10 µg/mL See Below Knockout Validated HIF-1 alpha/HIF1A is specifically detected in HeLa human cervical epithelial carcinoma parental cell line but is not detectable in HIF-1 alpha/HIF1A knockout HeLa cell line. DATA Western Blot Immunohistochemistry Detection of Human, Mouse, HIF-1 alpha/HIF1A in Human Kidney. and Rat HIF-1 alpha/HIF1A by HIF-1 alpha/HIF1A was detected in Western Blot. Western blot immersion fixed paraffin-embedded sections shows lysates of MCF-7 human of human kidney using Mouse Anti- breast cancer cell line, Balb-3T3 Human/Mouse/Rat HIF-1 alpha/HIF1A mouse embryonic fibroblast cell Monoclonal Antibody (Catalog # MAB1536) line, and PC-12 rat adrenal at 5 µg/mL for 1 hour at room temperature pheochromocytoma cell line followed by incubation with the Anti-Mouse untreated (-) or treated (+) with IgG VisUCyte™ HRP Polymer Antibody 150 μM CoCl2 for 8 hours. -
Early Growth Response 1 Acts As a Tumor Suppressor in Vivo and in Vitro Via Regulation of P53
Research Article Early Growth Response 1 Acts as a Tumor Suppressor In vivo and In vitro via Regulation of p53 Anja Krones-Herzig,1 Shalu Mittal,1 Kelly Yule,1 Hongyan Liang,2 Chris English,1 Rafael Urcis,1 Tarun Soni,1 Eileen D. Adamson,2 and Dan Mercola1,3 1Sidney Kimmel Cancer Center, San Diego, California and 2The Burnham Institute; 3Cancer Center, University of California at San Diego, La Jolla, California Abstract human tumor cell lines express little or no Egr1 in contrast to their normal counterparts (9–12). Furthermore, Egr1 is decreased or The early growth response 1 (Egr1) gene is a transcription factor that acts as both a tumor suppressor and a tumor undetectable in small cell lung tumors, human breast tumors promoter. Egr1-null mouse embryo fibroblasts bypass repli- (11, 13), and human gliomas (12). Reexpression of Egr1 in human tumor cells inhibits transformation. The mechanism of suppression cative senescence and exhibit a loss of DNA damage response h and an apparent immortal growth, suggesting loss of p53 involves the direct induction of TGF- 1 leading to an autocrine- functions. Stringent expression analysis revealed 266 tran- mediated suppression of transformation (8), increased fibronectin, scripts with >2-fold differential expression in Egr1-null mouse and plasminogen activator inhibitor (9). Egr1 also has been embryo fibroblasts, including 143 known genes. Of the 143 implicated in the regulation of p53 in human melanoma cells genes, program-assisted searching revealed 66 informative leading to apoptosis (14–16), and the proapoptotic tumor genes linked to Egr1. All 66 genes could be placed on a single suppressor gene PTEN also is directly regulated by Egr1 (17). -
The Transcription Factor Egr1 Is a Direct Regulator of Multiple Tumor
Cancer Gene Therapy (2006) 13, 115–124 r 2006 Nature Publishing Group All rights reserved 0929-1903/06 $30.00 www.nature.com/cgt REVIEW The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFb1, PTEN, p53, and fibronectin V Baron1, ED Adamson2, A Calogero3, G Ragona3 and D Mercola1,4,5 1Sidney Kimmel Cancer Center, San Diego, CA, USA; 2The Burnham Institute, La Jolla, CA, USA; 3The University of Rome, Rome, Italy; 4The Rebecca and John Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA and 5The Department of Pathology, University of California at Irvine, Irvine, CA, USA Recent studies are reviewed indicating that the transcription factor early growth response-1 (Egr1) is a direct regulator of multiple tumor suppressors including TGFb1, PTEN, p53, and fibronectin. The downstream pathways of these factors display multiple nodes of interaction with each other, suggesting the existence of a functional network of suppressor factors that serve to maintain normal growth regulation and resist the emergence of transformed variants. Paradoxically, Egr1 is oncogenic in prostate cancer. In the majority of these cancers, PTEN or p53 is inactive. It is suggested that these defects in the suppressor network allow for the unopposed induction of TGFb1 and fibronectin, which favor transformation and survival of prostate tumor epithelial cells, and explain the role of Egr1 in prostate cancer. Egr1 is a novel and logical target for intervention by gene therapy methods, and targeting methods are discussed. Cancer Gene Therapy (2006) 13, 115–124. doi:10.1038/sj.cgt.7700896; published online 2 September 2005 Keywords: suppressor network; anoikis; systems biology; prostate cancer; tumor progression Introduction products. -
Genomic Interaction Between ER and HMGB2 Identifies DDX18 As A
Oncogene (2015) 34, 3871–3880 © 2015 Macmillan Publishers Limited All rights reserved 0950-9232/15 www.nature.com/onc ORIGINAL ARTICLE Genomic interaction between ER and HMGB2 identifies DDX18 as a novel driver of endocrine resistance in breast cancer cells AM Redmond1,2, C Byrne1, FT Bane1, GD Brown2, P Tibbitts1,KO’Brien1, ADK Hill1, JS Carroll2 and LS Young1 Breast cancer resistance to endocrine therapies such as tamoxifen and aromatase inhibitors is a significant clinical problem. Steroid receptor coactivator-1 (SRC-1), a coregulatory protein of the oestrogen receptor (ER), has previously been shown to have a significant role in the progression of breast cancer. The chromatin protein high mobility group box 2 (HMGB2) was identified as an SRC-1 interacting protein in the endocrine-resistant setting. We investigated the expression of HMGB2 in a cohort of 1068 breast cancer patients and found an association with increased disease-free survival time in patients treated with endocrine therapy. However, it was also verified that HMGB2 expression could be switched on in endocrine-resistant tumours from breast cancer patients. To explore the function of this poorly characterized protein, we performed HMGB2 ChIPseq and found distinct binding patterns between the two contexts. In the resistant setting, the HMGB2, SRC-1 and ER complex are enriched at promoter regions of target genes, with bioinformatic analysis indicating a switch in binding partners between the sensitive and resistant phenotypes. Integration of binding and gene expression data reveals a concise set of target genes of this complex including the RNA helicase DDX18. Modulation of DDX18 directly affects growth of tamoxifen-resistant cells, suggesting that it may be a critical downstream effector of the HMGB2:ER complex. -
ETS1, Nfkb and AP1 Synergistically Transactivate the Human GM ± CSF Promoter
Oncogene (1997) 14, 2845 ± 2855 1997 Stockton Press All rights reserved 0950 ± 9232/97 $12.00 ETS1, NFkB and AP1 synergistically transactivate the human GM ± CSF promoter Ross S Thomas1, Martin J Tymms1, Leigh H McKinlay1, M Frances Shannon2, Arun Seth3 and Ismarl Kola1 1Molecular Genetics and Development Group, Institute of Reproduction and Development, Monash University, Melbourne 3168, Australia; 2Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide 5000, Australia; 3Department of Pathology, University of Toronto/Women's College Hospital, Toronto, Ontario, Canada Activation of helper T cells results in coordinate Activating signals ultimately result in cellular prolifera- expression of a number of cytokines involved in tion, and transcriptional induction and secretion of a dierentiation, proliferation and activation of the number of cytokines including IL-2 (interleukin-2), IL-3, haematopoietic system. Granulocyte-macrophage colony IFNg (interferon-gamma) and GM ± CSF (granulocyte- stimulating factor (GM ± CSF) is one such cytokine, macrophage colony-stimulating factor) (Stanley et al., whose increased expression results mostly from increases 1985; Miyajima et al., 1988; Arai et al., 1990). These in transcription. Cis-acting elements with NFkB, AP1 cytokines direct the eector functions of various cell and ETS-like binding motifs have been identi®ed in the types involved in an immune response, including B cells, promoter region of the GM ± CSF gene, and are macrophages, mast cells, eosinophils and neutrophils. important or essential for transcriptional activity follow- GM ± CSF expression in activated T cells is ing T cell activation. ETS1 is a transcription factor of regulated by two mechanisms. -
A Dissertation Entitled the Androgen Receptor
A Dissertation entitled The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit Submitted to the Graduate Faculty as partial fulfillment of the requirements for the PhD Degree in Biomedical science Dr. Manohar Ratnam, Committee Chair Dr. Lirim Shemshedini, Committee Member Dr. Robert Trumbly, Committee Member Dr. Edwin Sanchez, Committee Member Dr. Beata Lecka -Czernik, Committee Member Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo August 2011 Copyright 2011, Mesfin Gonit This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit As partial fulfillment of the requirements for the PhD Degree in Biomedical science The University of Toledo August 2011 Prostate cancer depends on the androgen receptor (AR) for growth and survival even in the absence of androgen. In the classical models of gene activation by AR, ligand activated AR signals through binding to the androgen response elements (AREs) in the target gene promoter/enhancer. In the present study the role of AREs in the androgen- independent transcriptional signaling was investigated using LP50 cells, derived from parental LNCaP cells through extended passage in vitro. LP50 cells reflected the signature gene overexpression profile of advanced clinical prostate tumors. The growth of LP50 cells was profoundly dependent on nuclear localized AR but was independent of androgen. Nevertheless, in these cells AR was unable to bind to AREs in the absence of androgen.