De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway
Identifieur interne : 000E49 ( Istex/Corpus ); précédent : 000E48; suivant : 000E50De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway
Auteurs : Raphaela Fritsche-Guenther ; Aurelia Noske ; Ute Ungethüm ; Ralf-Jürgen Kuban ; Peter M. Schlag ; Per-Ulf Tunn ; Janine Karle ; Veit Krenn ; Manfred Dietel ; Christine SersSource :
- Histopathology [ 0309-0167 ] ; 2010-12.
English descriptors
- KwdEn :
- EFNA1, EphA2, MAPK, osteosarcoma.
Abstract
Fritsche‐Guenther R, Noske A, Ungethüm U, Kuban R‐J, Schlag PM, Tunn P‐U, Karle J, Krenn V, Dietel M & Sers C (2010) Histopathology57, 836–850
Url:
DOI: 10.1111/j.1365-2559.2010.03713.x
Links to Exploration step
ISTEX:3DED41F38E4370408E0F64A502D887FC33CDB4ADLe document en format XML
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Schlag</name><affiliation><mods:affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Tunn, Per Lf" sort="Tunn, Per Lf" uniqKey="Tunn P" first="Per-Ulf" last="Tunn">Per-Ulf Tunn</name><affiliation><mods:affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Karle, Janine" sort="Karle, Janine" uniqKey="Karle J" first="Janine" last="Karle">Janine Karle</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Krenn, Veit" sort="Krenn, Veit" uniqKey="Krenn V" first="Veit" last="Krenn">Veit Krenn</name><affiliation><mods:affiliation>Center for Histology, Cytology and Molecular Diagnostic, Wissenschaftspark Trier, Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Dietel, Manfred" sort="Dietel, Manfred" uniqKey="Dietel M" first="Manfred" last="Dietel">Manfred Dietel</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Sers, Christine" sort="Sers, Christine" uniqKey="Sers C" first="Christine" last="Sers">Christine Sers</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:3DED41F38E4370408E0F64A502D887FC33CDB4AD</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1111/j.1365-2559.2010.03713.x</idno><idno type="url">https://api.istex.fr/document/3DED41F38E4370408E0F64A502D887FC33CDB4AD/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000E49</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000E49</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</title><author><name sortKey="Fritsche Uenther, Raphaela" sort="Fritsche Uenther, Raphaela" uniqKey="Fritsche Uenther R" first="Raphaela" last="Fritsche-Guenther">Raphaela Fritsche-Guenther</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Noske, Aurelia" sort="Noske, Aurelia" uniqKey="Noske A" first="Aurelia" last="Noske">Aurelia Noske</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Ungethum, Ute" sort="Ungethum, Ute" uniqKey="Ungethum U" first="Ute" last="Ungethüm">Ute Ungethüm</name><affiliation><mods:affiliation>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Kuban, Ralf Rgen" sort="Kuban, Ralf Rgen" uniqKey="Kuban R" first="Ralf-Jürgen" last="Kuban">Ralf-Jürgen Kuban</name><affiliation><mods:affiliation>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schlag, Peter M" sort="Schlag, Peter M" uniqKey="Schlag P" first="Peter M." last="Schlag">Peter M. Schlag</name><affiliation><mods:affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Tunn, Per Lf" sort="Tunn, Per Lf" uniqKey="Tunn P" first="Per-Ulf" last="Tunn">Per-Ulf Tunn</name><affiliation><mods:affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Karle, Janine" sort="Karle, Janine" uniqKey="Karle J" first="Janine" last="Karle">Janine Karle</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Krenn, Veit" sort="Krenn, Veit" uniqKey="Krenn V" first="Veit" last="Krenn">Veit Krenn</name><affiliation><mods:affiliation>Center for Histology, Cytology and Molecular Diagnostic, Wissenschaftspark Trier, Trier, Germany</mods:affiliation></affiliation></author><author><name sortKey="Dietel, Manfred" sort="Dietel, Manfred" uniqKey="Dietel M" first="Manfred" last="Dietel">Manfred Dietel</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Sers, Christine" sort="Sers, Christine" uniqKey="Sers C" first="Christine" last="Sers">Christine Sers</name><affiliation><mods:affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Histopathology</title><idno type="ISSN">0309-0167</idno><idno type="eISSN">1365-2559</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2010-12">2010-12</date><biblScope unit="volume">57</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="836">836</biblScope><biblScope unit="page" to="850">850</biblScope></imprint><idno type="ISSN">0309-0167</idno></series><idno type="istex">3DED41F38E4370408E0F64A502D887FC33CDB4AD</idno><idno type="DOI">10.1111/j.1365-2559.2010.03713.x</idno><idno type="ArticleID">HIS3713</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0309-0167</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>EFNA1</term><term>EphA2</term><term>MAPK</term><term>osteosarcoma</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Fritsche‐Guenther R, Noske A, Ungethüm U, Kuban R‐J, Schlag PM, Tunn P‐U, Karle J, Krenn V, Dietel M & Sers C (2010) Histopathology57, 836–850</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Raphaela Fritsche‐Guenther</name><affiliations><json:string>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Aurelia Noske</name><affiliations><json:string>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Ute Ungethüm</name><affiliations><json:string>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Ralf‐Jürgen Kuban</name><affiliations><json:string>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Peter M. Schlag</name><affiliations><json:string>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Per‐Ulf Tunn</name><affiliations><json:string>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Janine Karle</name><affiliations><json:string>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Veit Krenn</name><affiliations><json:string>Center for Histology, Cytology and Molecular Diagnostic, Wissenschaftspark Trier, Trier, Germany</json:string></affiliations></json:item><json:item><name>Manfred Dietel</name><affiliations><json:string>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Christine Sers</name><affiliations><json:string>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>EphA2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>EFNA1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MAPK</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>osteosarcoma</value></json:item></subject><articleId><json:string>HIS3713</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><qualityIndicators><score>5.288</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 782.362 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>142</abstractCharCount><pdfWordCount>6281</pdfWordCount><pdfCharCount>43545</pdfCharCount><pdfPageCount>15</pdfPageCount><abstractWordCount>24</abstractWordCount></qualityIndicators><title>De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</title><refBibs><json:item><host><pages><last>1468</last><first>1418</first></pages><author></author><title>Campanacci M. 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Chem.</title></host><title>Small molecules can selectively inhibit ephrin binding to the EphA4 and EphA2 receptors</title></json:item></refBibs><genre><json:string>article</json:string></genre><host><volume>57</volume><publisherId><json:string>HIS</json:string></publisherId><pages><total>15</total><last>850</last><first>836</first></pages><issn><json:string>0309-0167</json:string></issn><issue>6</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1365-2559</json:string></eissn><title>Histopathology</title><doi><json:string>10.1111/(ISSN)1365-2559</json:string></doi></host><categories><wos><json:string>science</json:string><json:string>pathology</json:string><json:string>cell biology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>pathology</json:string></scienceMetrix></categories><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1111/j.1365-2559.2010.03713.x</json:string></doi><id>3DED41F38E4370408E0F64A502D887FC33CDB4AD</id><score>0.26564786</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/3DED41F38E4370408E0F64A502D887FC33CDB4AD/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/3DED41F38E4370408E0F64A502D887FC33CDB4AD/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/3DED41F38E4370408E0F64A502D887FC33CDB4AD/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>© 2010 Blackwell Publishing Limited</p></availability><date>2010</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</title><author xml:id="author-1"><persName><forename type="first">Raphaela</forename><surname>Fritsche‐Guenther</surname></persName><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-2"><persName><forename type="first">Aurelia</forename><surname>Noske</surname></persName><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Ute</forename><surname>Ungethüm</surname></persName><affiliation>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Ralf‐Jürgen</forename><surname>Kuban</surname></persName><affiliation>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Peter M.</forename><surname>Schlag</surname></persName><affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">Per‐Ulf</forename><surname>Tunn</surname></persName><affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-7"><persName><forename type="first">Janine</forename><surname>Karle</surname></persName><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-8"><persName><forename type="first">Veit</forename><surname>Krenn</surname></persName><affiliation>Center for Histology, Cytology and Molecular Diagnostic, Wissenschaftspark Trier, Trier, Germany</affiliation></author><author xml:id="author-9"><persName><forename type="first">Manfred</forename><surname>Dietel</surname></persName><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author><author xml:id="author-10"><persName><forename type="first">Christine</forename><surname>Sers</surname></persName><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation></author></analytic><monogr><title level="j">Histopathology</title><idno type="pISSN">0309-0167</idno><idno type="eISSN">1365-2559</idno><idno type="DOI">10.1111/(ISSN)1365-2559</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2010-12"></date><biblScope unit="volume">57</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="836">836</biblScope><biblScope unit="page" to="850">850</biblScope></imprint></monogr><idno type="istex">3DED41F38E4370408E0F64A502D887FC33CDB4AD</idno><idno type="DOI">10.1111/j.1365-2559.2010.03713.x</idno><idno type="ArticleID">HIS3713</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Fritsche‐Guenther R, Noske A, Ungethüm U, Kuban R‐J, Schlag PM, Tunn P‐U, Karle J, Krenn V, Dietel M & Sers C (2010) Histopathology57, 836–850</p></abstract><abstract><p>De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</p></abstract><abstract><p>Aims: In osteosarcoma patients the development of metastases, often to the lungs, is the most frequent cause of death. The aim of this study was to elucidate the molecular mechanisms governing osteosarcoma development and dissemination and, thereby, to identify possible novel drug targets for improved treatment.</p></abstract><abstract><p>Methods and results: Osteosarcoma samples were characterized using genome‐wide microarrays: increased expression of the EphA2 receptor and its ligand EFNA1 was detected. In addition, increased expression of EFNB1, EFNB3 and EphA3 was suggested. Immunohistochemistry revealed an absence of EphA2 in normal bone, and de novo expression in osteosarcomas. EFNA1 was expressed in normal bone, but was significantly elevated in tumours. Further in vitro investigations on the functional role of EphA2 and EFNA1 showed that EFNA1 ligand binding induced increased tyrosine phoshorylation, receptor degradation and downstream mitogen‐activated protein kinase (MAPK) activation. Interference with the MAPK pathway unravelled a potential autoregulatory loop governing mainly EFNA1 expression via the same pathway.</p></abstract><abstract><p>Conclusion: Upregulation and de novo expression of ephrins in osteosarcomas are involved in oncogenic signalling and thus might stimulate osteosarcoma metastasis.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>EphA2</term></item><item><term>EFNA1</term></item><item><term>MAPK</term></item><item><term>osteosarcoma</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/3DED41F38E4370408E0F64A502D887FC33CDB4AD/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1365-2559</doi><issn type="print">0309-0167</issn><issn type="electronic">1365-2559</issn><idGroup><id type="product" value="HIS"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="HISTOPATHOLOGY">Histopathology</title></titleGroup></publicationMeta><publicationMeta level="part" position="12106"><doi origin="wiley">10.1111/his.2010.57.issue-6</doi><numberingGroup><numbering type="journalVolume" number="57">57</numbering><numbering type="journalIssue" number="6">6</numbering></numberingGroup><coverDate startDate="2010-12">December 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="7" status="forIssue"><doi origin="wiley">10.1111/j.1365-2559.2010.03713.x</doi><idGroup><id type="unit" value="HIS3713"></id></idGroup><countGroup><count type="pageTotal" number="15"></count></countGroup><titleGroup><title type="tocHeading1">Original Articles</title></titleGroup><copyright>© 2010 Blackwell Publishing Limited</copyright><eventGroup><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.4 mode:FullText" date="2010-12-17"></event><event type="firstOnline" date="2010-12-17"></event><event type="publishedOnlineFinalForm" date="2010-12-17"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-27"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-24"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="836">836</numbering><numbering type="pageLast" number="850">850</numbering></numberingGroup><correspondenceTo>R Fritsche, Charitè Universitätsmedizin Berlin, Institute of Pathology, Chariteplatz 1, D‐10117 Berlin, Germany. e‐mail: <email>raphaela.fritsche@charite.de</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:HIS.HIS3713.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Date of submission 5 August 2009 Accepted for publication 25 March 2010</unparsedEditorialHistory><countGroup><count type="figureTotal" number="7"></count><count type="tableTotal" number="4"></count></countGroup><titleGroup><title type="main"><i>De novo</i> expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</title><title type="shortAuthors"><i>R. Fritsche‐Guenther et al.</i></title><title type="short"><i>Ephrin expression in osteosarcoma</i></title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>Raphaela</givenNames><familyName>Fritsche‐Guenther</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Aurelia</givenNames><familyName>Noske</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a2"><personName><givenNames>Ute</givenNames><familyName>Ungethüm</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a2"><personName><givenNames>Ralf‐Jürgen</givenNames><familyName>Kuban</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a3"><personName><givenNames>Peter M.</givenNames><familyName>Schlag</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a3"><personName><givenNames>Per‐Ulf</givenNames><familyName>Tunn</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a1"><personName><givenNames>Janine</givenNames><familyName>Karle</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a4"><personName><givenNames>Veit</givenNames><familyName>Krenn</familyName></personName></creator><creator creatorRole="author" xml:id="cr9" affiliationRef="#a1"><personName><givenNames>Manfred</givenNames><familyName>Dietel</familyName></personName></creator><creator creatorRole="author" xml:id="cr10" affiliationRef="#a1"><personName><givenNames>Christine</givenNames><familyName>Sers</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="DE"><unparsedAffiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="DE"><unparsedAffiliation>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="DE"><unparsedAffiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</unparsedAffiliation></affiliation><affiliation xml:id="a4" countryCode="DE"><unparsedAffiliation>Center for Histology, Cytology and Molecular Diagnostic, Wissenschaftspark Trier, Trier, Germany</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">EphA2</keyword><keyword xml:id="k2">EFNA1</keyword><keyword xml:id="k3">MAPK</keyword><keyword xml:id="k4">osteosarcoma</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p>Fritsche‐Guenther R, Noske A, Ungethüm U, Kuban R‐J, Schlag PM, Tunn P‐U, Karle J, Krenn V, Dietel M & Sers C (2010) <i>Histopathology</i><b>57,</b> 836–850</p><p> <b><i>De novo</i> expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</b> </p><p><b>Aims: </b> In osteosarcoma patients the development of metastases, often to the lungs, is the most frequent cause of death. The aim of this study was to elucidate the molecular mechanisms governing osteosarcoma development and dissemination and, thereby, to identify possible novel drug targets for improved treatment.</p><p><b>Methods and results: </b> Osteosarcoma samples were characterized using genome‐wide microarrays: increased expression of the <i>EphA2</i> receptor and its ligand <i>EFNA1</i> was detected. In addition, increased expression of <i>EFNB1</i>, <i>EFNB3</i> and <i>EphA3</i> was suggested. Immunohistochemistry revealed an absence of EphA2 in normal bone, and <i>de novo</i> expression in osteosarcomas. EFNA1 was expressed in normal bone, but was significantly elevated in tumours. Further <i>in vitro</i> investigations on the functional role of EphA2 and EFNA1 showed that EFNA1 ligand binding induced increased tyrosine phoshorylation, receptor degradation and downstream mitogen‐activated protein kinase (MAPK) activation. Interference with the MAPK pathway unravelled a potential autoregulatory loop governing mainly EFNA1 expression via the same pathway.</p><p><b>Conclusion: </b> Upregulation and <i>de novo</i> expression of ephrins in osteosarcomas are involved in oncogenic signalling and thus might stimulate osteosarcoma metastasis.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Ephrin expression in osteosarcoma</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</title></titleInfo><name type="personal"><namePart type="given">Raphaela</namePart><namePart type="family">Fritsche‐Guenther</namePart><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aurelia</namePart><namePart type="family">Noske</namePart><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ute</namePart><namePart type="family">Ungethüm</namePart><affiliation>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ralf‐Jürgen</namePart><namePart type="family">Kuban</namePart><affiliation>Laboratory for Functional Genome Research, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter M.</namePart><namePart type="family">Schlag</namePart><affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Per‐Ulf</namePart><namePart type="family">Tunn</namePart><affiliation>Robert‐Rössle‐Klinikum, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Janine</namePart><namePart type="family">Karle</namePart><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Veit</namePart><namePart type="family">Krenn</namePart><affiliation>Center for Histology, Cytology and Molecular Diagnostic, Wissenschaftspark Trier, Trier, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Manfred</namePart><namePart type="family">Dietel</namePart><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Sers</namePart><affiliation>Institute of Pathology, Charitè Universitätsmedizin Berlin, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2010-12</dateIssued><edition>Date of submission 5 August 2009 Accepted for publication 25 March 2010</edition><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">7</extent><extent unit="tables">4</extent></physicalDescription><abstract>Fritsche‐Guenther R, Noske A, Ungethüm U, Kuban R‐J, Schlag PM, Tunn P‐U, Karle J, Krenn V, Dietel M & Sers C (2010) Histopathology57, 836–850</abstract><abstract>De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway</abstract><abstract>Aims: In osteosarcoma patients the development of metastases, often to the lungs, is the most frequent cause of death. The aim of this study was to elucidate the molecular mechanisms governing osteosarcoma development and dissemination and, thereby, to identify possible novel drug targets for improved treatment.</abstract><abstract>Methods and results: Osteosarcoma samples were characterized using genome‐wide microarrays: increased expression of the EphA2 receptor and its ligand EFNA1 was detected. In addition, increased expression of EFNB1, EFNB3 and EphA3 was suggested. Immunohistochemistry revealed an absence of EphA2 in normal bone, and de novo expression in osteosarcomas. EFNA1 was expressed in normal bone, but was significantly elevated in tumours. Further in vitro investigations on the functional role of EphA2 and EFNA1 showed that EFNA1 ligand binding induced increased tyrosine phoshorylation, receptor degradation and downstream mitogen‐activated protein kinase (MAPK) activation. Interference with the MAPK pathway unravelled a potential autoregulatory loop governing mainly EFNA1 expression via the same pathway.</abstract><abstract>Conclusion: Upregulation and de novo expression of ephrins in osteosarcomas are involved in oncogenic signalling and thus might stimulate osteosarcoma metastasis.</abstract><subject lang="en"><genre>keywords</genre><topic>EphA2</topic><topic>EFNA1</topic><topic>MAPK</topic><topic>osteosarcoma</topic></subject><relatedItem type="host"><titleInfo><title>Histopathology</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0309-0167</identifier><identifier type="eISSN">1365-2559</identifier><identifier type="DOI">10.1111/(ISSN)1365-2559</identifier><identifier type="PublisherID">HIS</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>57</number></detail><detail type="issue"><caption>no.</caption><number>6</number></detail><extent unit="pages"><start>836</start><end>850</end><total>15</total></extent></part></relatedItem><identifier type="istex">3DED41F38E4370408E0F64A502D887FC33CDB4AD</identifier><identifier type="DOI">10.1111/j.1365-2559.2010.03713.x</identifier><identifier type="ArticleID">HIS3713</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2010 Blackwell Publishing Limited</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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