Endothelin-2 Signaling in the Neural Retina Promotes the Endothelial Tip Cell State and Inhibits Angiogenesis
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Cellular Responses to Erbb-2 Overexpression in Human Mammary Luminal Epithelial Cells: Comparison of Mrna and Protein Expression
British Journal of Cancer (2004) 90, 173 – 181 & 2004 Cancer Research UK All rights reserved 0007 – 0920/04 $25.00 www.bjcancer.com Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression SL White1, S Gharbi1, MF Bertani1, H-L Chan1, MD Waterfield1 and JF Timms*,1 1 Ludwig Institute for Cancer Research, Wing 1.1, Cruciform Building, Gower Street, London WCIE 6BT, UK Microarray analysis offers a powerful tool for studying the mechanisms of cellular transformation, although the correlation between mRNA and protein expression is largely unknown. In this study, a microarray analysis was performed to compare transcription in response to overexpression of the ErbB-2 receptor tyrosine kinase in a model mammary luminal epithelial cell system, and in response to the ErbB-specific growth factor heregulin b1. We sought to validate mRNA changes by monitoring changes at the protein level using a parallel proteomics strategy, and report a surprisingly high correlation between transcription and translation for the subset of genes studied. We further characterised the identified targets and relate differential expression to changes in the biological properties of ErbB-2-overexpressing cells. We found differential regulation of several key cell cycle modulators, including cyclin D2, and downregulation of a large number of interferon-inducible genes, consistent with increased proliferation of the ErbB-2- overexpressing cells. Furthermore, differential expression of genes involved in extracellular matrix modelling and cellular adhesion was linked to altered adhesion of these cells. Finally, we provide evidence for enhanced autocrine activation of MAPK signalling and the AP-1 transcription complex. -
On the Turning of Xenopus Retinal Axons Induced by Ephrin-A5
Development 130, 1635-1643 1635 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00386 On the turning of Xenopus retinal axons induced by ephrin-A5 Christine Weinl1, Uwe Drescher2,*, Susanne Lang1, Friedrich Bonhoeffer1 and Jürgen Löschinger1 1Max-Planck-Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany 2MRC Centre for Developmental Neurobiology, King’s College London, New Hunt’s House, Guy’s Hospital Campus, London SE1 1UL, UK *Author for correspondence (e-mail: [email protected]) Accepted 13 January 2003 SUMMARY The Eph family of receptor tyrosine kinases and their turning or growth cone collapse when confronted with ligands, the ephrins, play important roles during ephrin-A5-Fc bound to beads. However, when added in development of the nervous system. Frequently they exert soluble form to the medium, ephrin-A5 induces growth their functions through a repellent mechanism, so that, for cone collapse, comparable to data from chick. example, an axon expressing an Eph receptor does not The analysis of growth cone behaviour in a gradient of invade a territory in which an ephrin is expressed. Eph soluble ephrin-A5 in the ‘turning assay’ revealed a receptor activation requires membrane-associated ligands. substratum-dependent reaction of Xenopus retinal axons. This feature discriminates ephrins from other molecules On fibronectin, we observed a repulsive response, with the sculpturing the nervous system such as netrins, slits and turning of growth cones away from higher concentrations class 3 semaphorins, which are secreted molecules. While of ephrin-A5. On laminin, retinal axons turned towards the ability of secreted molecules to guide axons, i.e. -
ADIPOR1 Is Essential for Vision and Its RPE Expression Is Lost in the Mfrp Valentin M Sluch
The Jackson Laboratory The Mouseion at the JAXlibrary Faculty Research 2018 Faculty Research 9-25-2018 ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrp Valentin M Sluch Angela Banks Hui Li Maura A Crowley Vanessa Davis See next page for additional authors Follow this and additional works at: https://mouseion.jax.org/stfb2018 Part of the Life Sciences Commons, and the Medicine and Health Sciences Commons Recommended Citation Sluch, Valentin M; Banks, Angela; Li, Hui; Crowley, Maura A; Davis, Vanessa; Xiang, Chuanxi; Yang, Junzheng; Demirs, John T; Vrouvlianis, Joanna; Leehy, Barrett; Hanks, Shawn; Hyman, Alexandra M; Aranda, Jorge; Chang, Bo; Bigelow, Chad E; and Rice, Dennis S, "ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrp" (2018). Faculty Research 2018. 197. https://mouseion.jax.org/stfb2018/197 This Article is brought to you for free and open access by the Faculty Research at The ousM eion at the JAXlibrary. It has been accepted for inclusion in Faculty Research 2018 by an authorized administrator of The ousM eion at the JAXlibrary. For more information, please contact [email protected]. Authors Valentin M Sluch, Angela Banks, Hui Li, Maura A Crowley, Vanessa Davis, Chuanxi Xiang, Junzheng Yang, John T Demirs, Joanna Vrouvlianis, Barrett Leehy, Shawn Hanks, Alexandra M Hyman, Jorge Aranda, Bo Chang, Chad E Bigelow, and Dennis S Rice This article is available at The ousM eion at the JAXlibrary: https://mouseion.jax.org/stfb2018/197 www.nature.com/scientificreports OPEN ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrprd6 mouse Received: 20 April 2018 Valentin M. -
Mir-146A Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells
G C A T T A C G G C A T genes Article MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells Yeojin Do 1, Jin Gu Cho 1, Ji Young Park 1, Sumin Oh 1, Doyeon Park 1 , Kyung Hyun Yoo 1,2 , Myeong-Sok Lee 1,2, Byung Su Kwon 3,* , Jongmin Kim 1,2,* and Young Yang 2,* 1 Division of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Korea; [email protected] (Y.D.); [email protected] (J.G.C.); [email protected] (J.Y.P.); [email protected] (S.O.); [email protected] (D.P.); [email protected] (K.H.Y.); [email protected] (M.-S.L.) 2 Research Institute for Women’s Health, Sookmyung Women’s University, Seoul 04310, Korea 3 Department of Obstetrics and Gynecology, Kyung Hee University Medical Center, 23, Seoul 02447, Korea * Correspondence: [email protected] (B.S.K.); [email protected] (J.K.); [email protected] (Y.Y.); Tel.: +82-2-958-8837 (B.S.K.); +82-2-710-9553 (J.K.); +82-2-710-9590 (Y.Y.) Abstract: Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. -
3B and Semaphorin-3F in Ovarian Cancer
Published OnlineFirst February 2, 2010; DOI: 10.1158/1535-7163.MCT-09-0664 Research Article Molecular Cancer Therapeutics Hormonal Regulation and Distinct Functions of Semaphorin- 3B and Semaphorin-3F in Ovarian Cancer Doina Joseph1, Shuk-Mei Ho2, and Viqar Syed1 Abstract Semaphorins comprise a family of molecules that influence neuronal growth and guidance. Class-3 sema- phorins, semaphorin-3B (SEMA3B) and semaphorin-3F (SEMA3F), illustrate their effects by forming a com- plex with neuropilins (NP-1 or NP-2) and plexins. We examined the status and regulation of semaphorins and their receptors in human ovarian cancer cells. A significantly reduced expression of SEMA3B (83 kDa), SE- MA3F (90 kDa), and plexin-A3 was observed in ovarian cancer cell lines when compared with normal human ovarian surface epithelial cells. The expression of NP-1, NP-2, and plexin-A1 was not altered in human ovar- ian surface epithelial and ovarian cancer cells. The decreased expression of SEMA3B, SEMA3F, and plexin-A3 was confirmed in stage 3 ovarian tumors. The treatment of ovarian cancer cells with luteinizing hormone, follicle-stimulating hormone, and estrogen induced a significant upregulation of SEMA3B, whereas SEMA3F was upregulated only by estrogen. Cotreatment of cell lines with a hormone and its specific antagonist blocked the effect of the hormone. Ectopic expression of SEMA3B or SEMA3F reduced soft-agar colony for- mation, adhesion, and cell invasion of ovarian cancer cell cultures. Forced expression of SEMA3B, but not SEMA3F, inhibited viability of ovarian cancer cells. Overexpression of SEMA3B and SEMA3F reduced focal adhesion kinase phosphorylation and matrix metalloproteinase-2 and matrix metalloproteinase-9 expression in ovarian cancer cells. -
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US 20080317666A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317666 A1 Fattal et al. (43) Pub. Date: Dec. 25, 2008 (54) COLONIC DELIVERY OF ACTIVE AGENTS Publication Classification (51) Int. Cl. (76) Inventors: Elias Fattal, Paris (FR); Antoine A6IR 9/00 (2006.01) Andremont, Malakoff (FR); A61R 49/00 (2006.01) Patrick Couvreur, A6II 5L/12 (2006.01) Villebon-sur-Yvette (FR); Sandrine A6IPI/00 (2006.01) Bourgeois, Lyon (FR) (52) U.S. Cl. .......................... 424/1.11; 424/423; 424/9.1 (57) ABSTRACT Correspondence Address: Drug delivery devices that are orally administered, and that David S. Bradlin release active ingredients in the colon, are disclosed. In one Womble Carlyle Sandridge & Rice embodiment, the active ingredients are those that inactivate P.O.BOX 7037 antibiotics, such as macrollides, quinolones and beta-lactam Atlanta, GA 30359-0037 (US) containing antibiotics. One example of a Suitable active agent is an enzyme Such as beta-lactamases. In another embodi ment, the active agents are those that specifically treat colonic (21) Appl. No.: 11/628,832 disorders, such as Chrohn's Disease, irritable bowel syn drome, ulcerative colitis, colorectal cancer or constipation. (22) PCT Filed: Feb. 9, 2006 The drug delivery devices are in the form of beads of pectin, crosslinked with calcium and reticulated with polyethylene imine. The high crosslink density of the polyethyleneimine is (86). PCT No.: PCT/GBO6/OO448 believed to stabilize the pectin beads for a sufficient amount of time such that a Substantial amount of the active ingredi S371 (c)(1), ents can be administered directly to the colon. -
Mechanisms of Skeletal Disease Mediated by Haematological
OF z a ) n Mechanisms of Skeletal Disease Mediated by Haematolo gical Malignancies Beiqing Pan B. Med. M. Med. Sc. Matthew Roberts Laboratory, Hanson Institute, Institute of Medical and Veterinary Science Department of Medicine, The University of Adelaide, South Australia A thesis submitted to the University of Adelaide in candidature for the degree of Doctor of Philosophy August 2004 TABLE OF CONTENTS DEGLARAT|ON......... """' l AGKNOWLEDGMENT.............. """' ll A8STRACT............. """'lv ABBREVIATIONS """""v1 PUBLICATIONS """"""'xl CHAPTER 1 GENERAL INTRODUCTION ......1 TO BONE 1.1 HAEMATOLOGICAL MALIGNANCIES WHICII GIBE RISE 1 LESIONS 2 1.1.1 Osteolytic Bone Disease Mediated by Multiple Myeloma 2 1.1.1.1 General Description...'.. 4 t.l.l.2 P athophysiolo gy of tvttvt 5 1.1.1.3 Osteolytic Bone Disease Lt.2 Osteoblastic Bone Disease Mediated by POEMS" 6 t.l.2.1 General DescriPtion...... 6 l.l.2.2 Pathophysiology of POEMS Syndrome. 1 8 1.1.2.3 Osteoblastic Bone Disease 1.2 BONE PHYSIOLOGY.............. 8 1.2.1 PhysiologicalBoneRemodelling 9 1.2.2 Bone ResorPtion 9 1.2.2.1 Osteoclasts 9 1.2.2.2 Osteoclast Stem Cells 1.2.3 BoneFormation.......'......... 1.2.3.1 Osteoblast Cells 1.2.3.2 OsteoblastStemCells..... 1.2.3.3 OsteocYtes '.".....' 1.2.3.4 Lining Cells FACTORS INVOLVED IN BONE LESIONS... t4 1.3 l6 1.3.1 Osteoclast Activating Factors (OAFÐ """"' 1.3.1.1 Interleukin-1P 16 1.3.1.2 Interleukin-6 t7 l8 1 .3.1 .3 Tumour Necrosis Factor-cx'...... 1.3.1.4 ParathyroidHormone Related Protein""""""' t9 1.3.2 RANKL/RANIIOPGSYStem 20 1.3.2.1 GeneralDescriPtion 20 1.3.2.2 RANKL/OPG Ratio and Bone Lesion 22 1.3.2.3 Incrçased RANKL/OPG Ratio in MM"' 22 1.3.2.4 The Regulation of RANKL/OPG Ratio in MM 23 1.3.3 Endothelin-1 (ET-l)'..'.'... -
Semaphorin Signaling Guides Cranial Neural Crest Cell Migration in Zebrafish
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Developmental Biology 280 (2005) 373–385 www.elsevier.com/locate/ydbio Semaphorin signaling guides cranial neural crest cell migration in zebrafish Hung-Hsiang Yu, Cecilia B. Moens* Howard Hughes Medical Institute and Division of Basic Science, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Box 19024 Seattle, WA 98109, USA Received for publication 2 December 2004, revised 19 January 2005, accepted 28 January 2005 Abstract Cranial neural crest cells (NCCs) migrate into the pharyngeal arches in three primary streams separated by two cranial neural crest (NC)- free zones. Multiple tissues have been implicated in the guidance of cranial NCC migration; however, the signals provided by these tissues have remained elusive. We investigate the function of semaphorins (semas) and their receptors, neuropilins (nrps), in cranial NCC migration in zebrafish. We find that genes of the sema3F and sema3G class are expressed in the cranial NC-free zones, while nrp2a and nrp2b are expressed in the migrating NCCs. sema3F/3G expression is expanded homogeneously in the head periphery through which the cranial NCCs migrate in lzr/pbx4 mutants, in which the cranial NC streams are fused. Antisense morpholino knockdown of Sema3F/3G or Nrp2 suppresses the abnormal cranial NC phenotype of lzr/pbx4 mutants, demonstrating that aberrant Sema3F/3G-Nrp2 signaling is responsible for this phenotype and suggesting that repulsive Sema3F/3G-Npn2 signaling normally contributes to the guidance of migrating cranial NCCs. Furthermore, global over-expression of sema3Gb phenocopies the aberrant cranial NC phenotype of lzr/pbx4 mutants when endogenous Sema3 ligands are knocked down, consistent with a model in which the patterned expression of Sema3 ligands in the head periphery coordinates the migration of Nrp-expressing cranial NCCs. -
Hepatocyte Growth Factor: a Regulator of Inflammation and Autoimmunity
Autoimmunity Reviews 14 (2015) 293–303 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev Review Hepatocyte growth factor: A regulator of inflammation and autoimmunity Nicolas Molnarfi a,b,1, Mahdia Benkhoucha a,b,1, Hiroshi Funakoshi d, Toshikazu Nakamura e, Patrice H. Lalive a,b,c,⁎ a Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland b Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, University Hospital of Geneva, Geneva, Switzerland c Department of Genetics and Laboratory Medicine, Laboratory Medicine Service, University Hospital of Geneva, Geneva, Switzerland d Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa, Japan e Neurogen Inc., Nakahozumi, Ibaraki, Osaka, Japan article info abstract Article history: Hepatocyte growth factor (HGF) is a pleiotropic cytokine that has been extensively studied over several decades, Received 20 November 2014 but was only recently recognized as a key player in mediating protection of many types of inflammatory and au- Accepted 25 November 2014 toimmune diseases. HGF was reported to prevent and attenuate disease progression by influencing multiple Available online 1 December 2014 pathophysiological processes involved in inflammatory and immune response, including cell migration, matura- tion, cytokine production, antigen presentation, and T cell effector function. In this review, we discuss the actions Keywords: fl HGF and mechanisms of HGF in in ammation and immunity and the therapeutic potential of this factor for the treat- fl c-Met ment of in ammatory and autoimmune diseases. Inflammation © 2014 Elsevier B.V. All rights reserved. Autoimmunity Autoimmune regulator Therapy Contents 1. -
1,25-Dihydroxyvitamin D3-Induced Genes in Osteoblasts
1,25-DIHYDROXYVITAMIN D3-INDUCED GENES IN OSTEOBLASTS: UNCOVERING NEW FUNCTIONS FOR MENINGIOMA 1 AND SEMAPHORIN 3B IN SKELETAL PHYSIOLOGY by XIAOXUE ZHANG Submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Thesis advisor: Paul N. MacDonald Department of Pharmacology CASE WESTERN RESERVE UNIVERSITY May 2009 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of _____________________________________________________ candidate for the ______________________degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. I dedicate this thesis to my mother and father for their lifelong love, encouragement and sacrifice TABLE OF CONTENTS Table of Contents ii List of Tables iii List of Figures iv Acknowledgements vii Abbreviations x Abstract xiii Chapter I Introduction 1 Chapter II Meningioma 1 (MN1) is a 1,25-dihydroxyvitamin D3- 44 induced transcription coactivator that promotes osteoblast proliferation, motility, differentiation, and function Chapter III Semaphorin 3B (SEMA3B) is a 1,25- 108 dihydroxyvitamin D3-induced gene in osteoblasts that promotes -
FGF8 Signaling Regulates Growth of Midbrain Dopaminergic Axons by Inducing Semaphorin 3F
4044 • The Journal of Neuroscience, April 1, 2009 • 29(13):4044–4055 Development/Plasticity/Repair FGF8 Signaling Regulates Growth of Midbrain Dopaminergic Axons by Inducing Semaphorin 3F Kenta Yamauchi,1* Shigeki Mizushima,1* Atsushi Tamada,2 Nobuhiko Yamamoto,1 Seiji Takashima,3 and Fujio Murakami1,2 1Laboratory of Neuroscience, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan, 2Division of Behavior and Neurobiology, National Institute for Basic Biology, Okazaki 444-8585, Japan, and 3Department of Molecular Cardiology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan Accumulating evidence indicates that signaling centers controlling the dorsoventral (DV) polarization of the neural tube, the roof plate and the floor plate, play crucial roles in axon guidance along the DV axis. However, the role of signaling centers regulating the rostrocau- dal (RC) polarization of the neural tube in axon guidance along the RC axis remains unknown. Here, we show that a signaling center located at the midbrain–hindbrain boundary (MHB) regulates the rostrally directed growth of axons from midbrain dopaminergic neurons (mDANs). We found that beads soaked with fibroblast growth factor 8 (FGF8), a signaling molecule that mediates patterning activities of the MHB, repelled mDAN axons that extended through the diencephalon. This repulsion may be mediated by semaphorin 3F (sema3F) because (1) FGF8-soaked beads induced an increase in expression of sema3F, (2) sema3F expression in the midbrain was essentially abolished by the application of an FGF receptor tyrosine kinase inhibitor, and (3) mDAN axonal growth was also inhibited by sema3F. Furthermore, mDAN axons expressed a sema3F receptor, neuropilin-2 (nrp2), and the removal ofnrp-2 by gene targeting caused caudal growth of mDAN axons. -
Neuropilin-1 Conveys Semaphorin and VEGF Signaling During Neural and Cardiovascular Development
Developmental Cell, Vol. 5, 45–57, July, 2003, Copyright 2003 by Cell Press Neuropilin-1 Conveys Semaphorin and VEGF Signaling during Neural and Cardiovascular Development Chenghua Gu,1,2 E. Rene Rodriguez,3 capable of mediating a variety of protein/protein interac- Dorothy V. Reimert,1,2 Tianzhi Shu,4 tions (Fujisawa et al., 1997). While Npn-1 can mediate Bernd Fritzsch,5 Linda J. Richards,4 heterophilic cell adhesion (Fujisawa et al., 1997; Shimizu Alex L. Kolodkin,1,* and David D. Ginty1,2,* et al., 2000), it is also the ligand binding subunit of the 1Department of Neuroscience semaphorin 3A/collapsin-1 (Sema3A) receptor complex 2 Howard Hughes Medical Institute (He and Tessier-Lavigne, 1997; Kolodkin et al., 1997). 3 Department of Pathology Semaphorins comprise a large family of proteins first The Johns Hopkins University School of Medicine described as regulators of axon pathfinding (Huber et 725 North Wolfe Street al., 2003). Class 3 semaphorins, including Sema3A, are Baltimore, Maryland 21205 secreted vertebrate semaphorins that can act as potent 4 Department of Anatomy and Neurobiology axon repellents for specific populations of neurons. School of Medicine These ligands appear to exert their chemorepulsive ef- The University of Maryland, Baltimore fects via receptor complexes which include the ligand Baltimore, Maryland 21201 binding subunit Npn-1, or its close family member 5 Department of Biomedical Sciences Npn-2, and a signal transducing subunit consisting of Creighton University one of four class A plexin proteins (He et al., 2002). Omaha, Nebraska 68178 Six class 3 secreted semaphorins have been identified, Sema3A, 3B, 3C, 3D, 3E, and 3F, and each of these ligands can bind with high affinity to either Npn-1, Npn-2, Summary or to both.