EGR-1 is regulated by N-methyl-D-aspartate-receptor stimulation and associated with patient survival in human high grade astrocytomas

Autoren

Michel Mittelbronn
Patrick Harter
Arne Warth
Adrian Lupescu
Karin Schilbach
Henning Vollmann
David Capper
Benjamin Goeppert
Karl Frei
Helmut Bertalanffy
Michael Weller
Richard Meyermann
Florian Lang
Perikles Simon

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000263909100003&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.1111/j.1750-3639.2008.00175.x

Externe Identifier

Clarivate Analytics Document Solution ID: 415BK
PubMed Identifier: 18489490

ISSN

1015-6305

Ausgabe der Veröffentlichung

2

Zeitschrift

BRAIN PATHOLOGY

Schlüsselwörter

Astrocytomas
EGR-1
NMDA-R

Paginierung

195 - 204

Datum der Veröffentlichung

2009

Status

Published

Titel

EGR-1 is Regulated by N-Methyl-D-Aspartate-Receptor Stimulation and Associated with Patient Survival in Human High Grade Astrocytomas

Sub types

Article

Ausgabe der Zeitschrift

19

Datenquelle: Web of Science (Lite)

Abstract

AbstractEarly growth response‐1 (EGR‐1) is considered a central regulator in tumor cell proliferation, migration and angiogenesis and a promising candidate for gene therapy in human astrocytomas. However, conflicting data have been reported suggesting that both tumor promoting and anti‐tumor activity of EGR‐1 and its regulation, expression and prognostic significance still remain enigmatic. Our study explored EGR‐1 expression and regulation in astrocytomas and its association with patient survival. As we detected two EGR‐1 mRNA variants, one containing a N‐methyl‐D‐aspartate‐receptor (NMDA‐R) responsive cytoplasmic polyadenylation element (CPE), further experiments were performed to determine the functional role of this pathway. After NMDA stimulation of SV‐FHAS and neoplastic astrocytes, real‐time polymerase chain reaction showed an increase of the CPE, containing EGR‐1 splice variant only in astrocytoma cells. The surface expression and functionality of NMDA‐R were demonstrated by flow cytometric analysis and measurement of increased intracellular Ca2+. EGR‐1 was mainly restricted to tumor cells expressing NMDA‐R and significantly up‐regulated in astrocytic tumors compared with normal brain. Further, EGR‐1 expression was significantly (P < 0.007) associated with enhanced patient survival and was an independent prognostic factor in multivariate analysis in high grade astrocytomas. The NMDA‐R‐mediated EGR‐1 expression, therefore, seems to be a promising target for novel clinical approaches to astrocytoma treatment.

Autoren

Michel Mittelbronn
Patrick Harter
Arne Warth
Adrian Lupescu
Karin Schilbach
Henning Vollmann
David Capper
Benjamin Goeppert
Karl Frei
Helmut Bertalanffy
Michael Weller
Richard Meyermann
Florian Lang
Perikles Simon

DOI

10.1111/j.1750-3639.2008.00175.x

eISSN

1750-3639

ISSN

1015-6305

Ausgabe der Veröffentlichung

2

Zeitschrift

Brain Pathology

Sprache

en

Online publication date

2009

Paginierung

195 - 204

Datum der Veröffentlichung

2009

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1111/j.1750-3639.2008.00175.x

Datum der Datenerfassung

2023

Titel

EGR‐1 is Regulated by N‐Methyl‐D‐Aspartate‐Receptor Stimulation and Associated with Patient Survival in Human High Grade Astrocytomas

Ausgabe der Zeitschrift

19

Datenquelle: Crossref

Abstract

Early growth response-1 (EGR-1) is considered a central regulator in tumor cell proliferation, migration and angiogenesis and a promising candidate for gene therapy in human astrocytomas. However, conflicting data have been reported suggesting that both tumor promoting and anti-tumor activity of EGR-1 and its regulation, expression and prognostic significance still remain enigmatic. Our study explored EGR-1 expression and regulation in astrocytomas and its association with patient survival. As we detected two EGR-1 mRNA variants, one containing a N-methyl-D-aspartate-receptor (NMDA-R) responsive cytoplasmic polyadenylation element (CPE), further experiments were performed to determine the functional role of this pathway. After NMDA stimulation of SV-FHAS and neoplastic astrocytes, real-time polymerase chain reaction showed an increase of the CPE, containing EGR-1 splice variant only in astrocytoma cells. The surface expression and functionality of NMDA-R were demonstrated by flow cytometric analysis and measurement of increased intracellular Ca(2+). EGR-1 was mainly restricted to tumor cells expressing NMDA-R and significantly up-regulated in astrocytic tumors compared with normal brain. Further, EGR-1 expression was significantly (P < 0.007) associated with enhanced patient survival and was an independent prognostic factor in multivariate analysis in high grade astrocytomas. The NMDA-R-mediated EGR-1 expression, therefore, seems to be a promising target for novel clinical approaches to astrocytoma treatment.

Addresses

Institute of Brain Research, University of Tübingen, Tübingen, Germany. mittelbronn@usz.ch

Autoren

Michel Mittelbronn
Patrick Harter
Arne Warth
Adrian Lupescu
Karin Schilbach
Henning Vollmann
David Capper
Benjamin Goeppert
Karl Frei
Helmut Bertalanffy
Michael Weller
Richard Meyermann
Florian Lang
Perikles Simon

DOI

10.1111/j.1750-3639.2008.00175.x

eISSN

1750-3639

Externe Identifier

PubMed Identifier: 18489490
PubMed Central ID: PMC8094652

Open access

false

ISSN

1015-6305

Ausgabe der Veröffentlichung

2

Zeitschrift

Brain pathology (Zurich, Switzerland)

Schlüsselwörter

Brain
Cell Line, Tumor
Tumor Cells, Cultured
Humans
Astrocytoma
Glioblastoma
Brain Neoplasms
Calcium
N-Methylaspartate
Receptors, N-Methyl-D-Aspartate
Protein Isoforms
RNA, Messenger
Fluorescent Antibody Technique
Flow Cytometry
Immunohistochemistry
Multivariate Analysis
Polymerase Chain Reaction
Gene Expression Regulation, Neoplastic
Early Growth Response Protein 1
Kaplan-Meier Estimate

Sprache

eng

Medium

Print-Electronic

Online publication date

2008

Paginierung

195 - 204

Datum der Veröffentlichung

2009

Status

Published

Datum der Datenerfassung

2008

Titel

EGR-1 is regulated by N-methyl-D-aspartate-receptor stimulation and associated with patient survival in human high grade astrocytomas.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

19

Files

https://europepmc.org/articles/PMC8094652?pdf=render

Datenquelle: Europe PubMed Central

Abstract

Early growth response-1 (EGR-1) is considered a central regulator in tumor cell proliferation, migration and angiogenesis and a promising candidate for gene therapy in human astrocytomas. However, conflicting data have been reported suggesting that both tumor promoting and anti-tumor activity of EGR-1 and its regulation, expression and prognostic significance still remain enigmatic. Our study explored EGR-1 expression and regulation in astrocytomas and its association with patient survival. As we detected two EGR-1 mRNA variants, one containing a N-methyl-D-aspartate-receptor (NMDA-R) responsive cytoplasmic polyadenylation element (CPE), further experiments were performed to determine the functional role of this pathway. After NMDA stimulation of SV-FHAS and neoplastic astrocytes, real-time polymerase chain reaction showed an increase of the CPE, containing EGR-1 splice variant only in astrocytoma cells. The surface expression and functionality of NMDA-R were demonstrated by flow cytometric analysis and measurement of increased intracellular Ca(2+). EGR-1 was mainly restricted to tumor cells expressing NMDA-R and significantly up-regulated in astrocytic tumors compared with normal brain. Further, EGR-1 expression was significantly (P < 0.007) associated with enhanced patient survival and was an independent prognostic factor in multivariate analysis in high grade astrocytomas. The NMDA-R-mediated EGR-1 expression, therefore, seems to be a promising target for novel clinical approaches to astrocytoma treatment.

Autoren

Michel Mittelbronn
Patrick Harter
Arne Warth
Adrian Lupescu
Karin Schilbach
Henning Vollmann
David Capper
Benjamin Goeppert
Karl Frei
Helmut Bertalanffy
Michael Weller
Richard Meyermann
Florian Lang
Perikles Simon

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/18489490

DOI

10.1111/j.1750-3639.2008.00175.x

eISSN

1750-3639

Externe Identifier

PubMed Central ID: PMC8094652

Ausgabe der Veröffentlichung

2

Zeitschrift

Brain Pathol

Schlüsselwörter

Astrocytoma
Brain
Brain Neoplasms
Calcium
Cell Line, Tumor
Early Growth Response Protein 1
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic
Glioblastoma
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Multivariate Analysis
N-Methylaspartate
Polymerase Chain Reaction
Protein Isoforms
RNA, Messenger
Receptors, N-Methyl-D-Aspartate
Tumor Cells, Cultured

Sprache

eng

Country

Switzerland

Paginierung

195 - 204

PII

BPA175

Datum der Veröffentlichung

2009

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2009

Titel

EGR-1 is regulated by N-methyl-D-aspartate-receptor stimulation and associated with patient survival in human high grade astrocytomas.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

19

Datenquelle: PubMed

EGR-1 is regulated by N-methyl-D-aspartate-receptor stimulation and associated with patient survival in human high grade astrocytomas

Files

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