PMID: 9177251Jun 10, 1997Paper

Cell-surface perturbations of the epidermal growth factor and vascular endothelial growth factor receptors by phosphorothioate oligodeoxynucleotides

Proceedings of the National Academy of Sciences of the United States of America
P RockwellC A Stein

Abstract

Antisense oligodeoxynucleotides offer potential as therapeutic agents to inhibit gene expression. Recent evidence indicates that oligodeoxynucleotides designed to target specific nucleic acid sequences can interact nonspecifically with proteins. This report describes the interactive capabilities of phosphorothioate oligodeoxynucleotides of defined sequence and length with two essential protein tyrosine receptors, flk-1 and epidermal growth factor receptor (EGFR), and their effects on receptor signaling in a transfected and tumor cell line, respectively. Phosphorothioate oligodeoxynucleotides bound to the cell surface, as demonstrated by fluorescence-activated cell-sorter analyses (FACS), and perturbed receptor activation in the presence and absence of cognate ligands, EGF (EGFR) and vascular endothelial growth factor (flk-1), in phosphorylation assays. Certain phosphorothioate oligodeoxynucleotides interacted relatively selectively with flk-1 and partially blocked the binding of specific anti-receptor monoclonal antibodies to target sites. They stimulated EGFR phosphorylation in the absence of EGF but antagonized ligand-mediated activation of EGFR and flk-1. In vivo studies showed that a nonspecific phosphorothioate oligodeoxyn...Continue Reading

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Citations

Jul 7, 2009·Applied Microbiology and Biotechnology·Masashi HatamotoHiroyuki Imachi
Jul 13, 2001·Pharmacology & Therapeutics·C J Wraight, P J White
Mar 31, 2000·Pharmacology & Therapeutics·C A Stein
Jun 7, 2000·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·I LebedevaM Vilenchik
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Johnathan C LaiCy A Stein
Apr 16, 2003·European Journal of Biochemistry·Jens Kurreck
May 21, 1998·Antisense & Nucleic Acid Drug Development·C A Stein
Jan 7, 2006·Oligonucleotides·Eckart MatthesMartin Von Janta-Lipinski
Apr 25, 2002·Nucleic Acids Research·Jens KurreckVolker A Erdmann
Dec 18, 2004·Nucleic Acids Research·Denis DryginC Frank Bennett
Apr 24, 2009·Nucleic Acids Research·Stefan KippenbergerAugust Bernd
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·I Lebedeva, C A Stein
Nov 24, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·I V Lebedeva, C A Stein
Dec 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·N ShiW M Pardridge
May 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Johnathan C LaiC A Stein
Feb 26, 2009·Expert Opinion on Drug Delivery·Mei Lin TanCrispin R Dass
Nov 17, 2004·Journal of Drug Targeting·Ian R GilmoreSaghir Akhtar
Mar 29, 2002·The Journal of Investigative Dermatology·Usha NagavarapuG Scott Herron
Mar 30, 2004·Clinical Prostate Cancer·Luba Benimetskaya, C A Stein
May 6, 2008·British Journal of Pharmacology·V L BensonH C Lowe
Sep 24, 2004·Trends in Pharmacological Sciences·Scott P HenryNicholas M Dean
Jun 16, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fuxin Shi, Dick Hoekstra
May 23, 2006·Cancer Treatment Reviews·Carsten NiederMichael Molls
Dec 13, 2005·Seminars in Oncology·C A SteinS Mani
Mar 11, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniela CastanottoCy A Stein
Sep 7, 2001·The Journal of Clinical Investigation·C A Stein

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