c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme
Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase A...
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| Veröffentlicht in: | The Journal of pathology 2009-07, Vol.218 (3), p.292-300 |
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| creator | Snyder, Eric L Sandstrom, Deborah J Law, Kenneth Fiore, Christopher Sicinska, Ewa Brito, Joseph Bailey, Dyane Fletcher, Jonathan A Loda, Massimo Rodig, Scott J Dal Cin, Paola Fletcher, Christopher DM |
| description | Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/path.2564 |
| format | Article |
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To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.2564</identifier><identifier>PMID: 19449367</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adipocytes - pathology ; Animals ; Biological and medical sciences ; c-Jun ; c-Jun protein ; Cell Differentiation - physiology ; Cell Line, Tumor ; Cell number ; Chromosomes ; dedifferentiation ; Dermatology ; Differentiation ; Disease Progression ; Evolution ; Fluorescence in situ hybridization ; Gene Amplification ; Genes, jun ; genomics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Investigative techniques, diagnostic techniques (general aspects) ; Liposarcoma ; Liposarcoma - genetics ; Liposarcoma - metabolism ; Liposarcoma - pathology ; MAP kinase ; MAP Kinase Kinase Kinase 5 - metabolism ; MDM2 protein ; Medical sciences ; Mice ; Mice, Nude ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Proto-Oncogene Proteins c-jun - metabolism ; Transcription factors ; Tumors of the skin and soft tissue. Premalignant lesions</subject><ispartof>The Journal of pathology, 2009-07, Vol.218 (3), p.292-300</ispartof><rights>Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><rights>2009 INIST-CNRS</rights><rights>2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4824-2f9f1ad0a735ee46ee2ad771048a2fc6e902fc6885b8e76b16afc39faca6e40c3</citedby><cites>FETCH-LOGICAL-c4824-2f9f1ad0a735ee46ee2ad771048a2fc6e902fc6885b8e76b16afc39faca6e40c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.2564$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.2564$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21562802$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19449367$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Snyder, Eric L</creatorcontrib><creatorcontrib>Sandstrom, Deborah J</creatorcontrib><creatorcontrib>Law, Kenneth</creatorcontrib><creatorcontrib>Fiore, Christopher</creatorcontrib><creatorcontrib>Sicinska, Ewa</creatorcontrib><creatorcontrib>Brito, Joseph</creatorcontrib><creatorcontrib>Bailey, Dyane</creatorcontrib><creatorcontrib>Fletcher, Jonathan A</creatorcontrib><creatorcontrib>Loda, Massimo</creatorcontrib><creatorcontrib>Rodig, Scott J</creatorcontrib><creatorcontrib>Dal Cin, Paola</creatorcontrib><creatorcontrib>Fletcher, Christopher DM</creatorcontrib><title>c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><subject>Adipocytes - pathology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>c-Jun</subject><subject>c-Jun protein</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Line, Tumor</subject><subject>Cell number</subject><subject>Chromosomes</subject><subject>dedifferentiation</subject><subject>Dermatology</subject><subject>Differentiation</subject><subject>Disease Progression</subject><subject>Evolution</subject><subject>Fluorescence in situ hybridization</subject><subject>Gene Amplification</subject><subject>Genes, jun</subject><subject>genomics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Liposarcoma</subject><subject>Liposarcoma - genetics</subject><subject>Liposarcoma - metabolism</subject><subject>Liposarcoma - pathology</subject><subject>MAP kinase</subject><subject>MAP Kinase Kinase Kinase 5 - metabolism</subject><subject>MDM2 protein</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Proto-Oncogene Proteins c-jun - metabolism</subject><subject>Transcription factors</subject><subject>Tumors of the skin and soft tissue. Premalignant lesions</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQxiMEokvhwAuALwVxSGs7iRMfq0Jb0ApWaqtys2ad8a4hiYOd0O5j8MY4ZFVOcBr_-c33zehLkpeMHjNK-UkPw_aYFyJ_lCwYlSKVlRSPk0X842mWs_IgeRbCN0qplEXxNDlgMs9lJspF8kunn8aOQNs31lgNg3Xx1tXE_USP973HEP48eSSu026DndXEdqSxvQvgtWuBrMeBdG4g0NzBLpAwmihlsRvI4CK7tWsbj1skUMcuvRuiRG2NiQ7dYGfP3ruNh7bF58kTA03AF_t6mNycf7g-u0yXXy4-np0uU51XPE-5kYZBTaHMCsRcIHKoy5LRvAJutEBJp1JVxbrCUqyZAKMzaUCDwJzq7DB5O-tG5x8jhkG1NmhsGujQjUFJWjJRSJZH8s1_SRFHYLysIvhuBrV3IXg0qve2Bb9TjKopKTUlpaakIvtqLzquW6z_kvtoInC0ByBoaIyHTtvwwHFWCF5RHrmTmbuzDe7-7ahWp9eXe-t07rBhwPuHDvDfp1XKQt1-vlCr1e1V9vX8vVpG_vXMG3AKNj5OcXPFKcsoi2osLv4bR17Hpw</recordid><startdate>200907</startdate><enddate>200907</enddate><creator>Snyder, Eric L</creator><creator>Sandstrom, Deborah J</creator><creator>Law, Kenneth</creator><creator>Fiore, Christopher</creator><creator>Sicinska, Ewa</creator><creator>Brito, Joseph</creator><creator>Bailey, Dyane</creator><creator>Fletcher, Jonathan A</creator><creator>Loda, Massimo</creator><creator>Rodig, Scott J</creator><creator>Dal Cin, Paola</creator><creator>Fletcher, Christopher DM</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>FBQ</scope><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TO</scope><scope>H94</scope></search><sort><creationdate>200907</creationdate><title>c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme</title><author>Snyder, Eric L ; Sandstrom, Deborah J ; Law, Kenneth ; Fiore, Christopher ; Sicinska, Ewa ; Brito, Joseph ; Bailey, Dyane ; Fletcher, Jonathan A ; Loda, Massimo ; Rodig, Scott J ; Dal Cin, Paola ; Fletcher, Christopher DM</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4824-2f9f1ad0a735ee46ee2ad771048a2fc6e902fc6885b8e76b16afc39faca6e40c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adipocytes - pathology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>c-Jun</topic><topic>c-Jun protein</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Line, Tumor</topic><topic>Cell number</topic><topic>Chromosomes</topic><topic>dedifferentiation</topic><topic>Dermatology</topic><topic>Differentiation</topic><topic>Disease Progression</topic><topic>Evolution</topic><topic>Fluorescence in situ hybridization</topic><topic>Gene Amplification</topic><topic>Genes, jun</topic><topic>genomics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Liposarcoma</topic><topic>Liposarcoma - genetics</topic><topic>Liposarcoma - metabolism</topic><topic>Liposarcoma - pathology</topic><topic>MAP kinase</topic><topic>MAP Kinase Kinase Kinase 5 - metabolism</topic><topic>MDM2 protein</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Proto-Oncogene Proteins c-jun - metabolism</topic><topic>Transcription factors</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Snyder, Eric L</creatorcontrib><creatorcontrib>Sandstrom, Deborah J</creatorcontrib><creatorcontrib>Law, Kenneth</creatorcontrib><creatorcontrib>Fiore, Christopher</creatorcontrib><creatorcontrib>Sicinska, Ewa</creatorcontrib><creatorcontrib>Brito, Joseph</creatorcontrib><creatorcontrib>Bailey, Dyane</creatorcontrib><creatorcontrib>Fletcher, Jonathan A</creatorcontrib><creatorcontrib>Loda, Massimo</creatorcontrib><creatorcontrib>Rodig, Scott J</creatorcontrib><creatorcontrib>Dal Cin, Paola</creatorcontrib><creatorcontrib>Fletcher, Christopher DM</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Snyder, Eric L</au><au>Sandstrom, Deborah J</au><au>Law, Kenneth</au><au>Fiore, Christopher</au><au>Sicinska, Ewa</au><au>Brito, Joseph</au><au>Bailey, Dyane</au><au>Fletcher, Jonathan A</au><au>Loda, Massimo</au><au>Rodig, Scott J</au><au>Dal Cin, Paola</au><au>Fletcher, Christopher DM</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2009-07</date><risdate>2009</risdate><volume>218</volume><issue>3</issue><spage>292</spage><epage>300</epage><pages>292-300</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><abstract>Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>19449367</pmid><doi>10.1002/path.2564</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes - pathology Animals Biological and medical sciences c-Jun c-Jun protein Cell Differentiation - physiology Cell Line, Tumor Cell number Chromosomes dedifferentiation Dermatology Differentiation Disease Progression Evolution Fluorescence in situ hybridization Gene Amplification Genes, jun genomics Humans Immunohistochemistry In Situ Hybridization, Fluorescence Investigative techniques, diagnostic techniques (general aspects) Liposarcoma Liposarcoma - genetics Liposarcoma - metabolism Liposarcoma - pathology MAP kinase MAP Kinase Kinase Kinase 5 - metabolism MDM2 protein Medical sciences Mice Mice, Nude Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Proto-Oncogene Proteins c-jun - metabolism Transcription factors Tumors of the skin and soft tissue. Premalignant lesions |
| title | c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme |
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