High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and sm...
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| Veröffentlicht in: | Experimental and molecular pathology 2013-04, Vol.94 (2), p.314-321 |
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| creator | Hapkova, Ilona Skarda, Josef Rouleau, Caroline Thys, An Notarnicola, Cécile Janikova, Maria Bernex, Florence Rypka, Miroslav Vanderwinden, Jean-Marie Faure, Sandrine Vesely, Jaroslav de Santa Barbara, Pascal |
| description | Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n=23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p |
| doi_str_mv | 10.1016/j.yexmp.2012.12.004 |
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GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n=23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p<0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.</description><identifier>ISSN: 0014-4800</identifier><identifier>EISSN: 1096-0945</identifier><identifier>DOI: 10.1016/j.yexmp.2012.12.004</identifier><identifier>PMID: 23295309</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Adult ; Aged ; Amino Acid Sequence ; Cell Line, Tumor ; Female ; Gastrointestinal Neoplasms - genetics ; Gastrointestinal Neoplasms - metabolism ; Gastrointestinal stromal tumors (GIST) ; Gastrointestinal Stromal Tumors - genetics ; Gastrointestinal Stromal Tumors - metabolism ; Gastrointestinal Tract - metabolism ; Gene Expression ; HEK293 Cells ; Human health and pathology ; Humans ; Interstitial cell of Cajal ; Life Sciences ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Proto-Oncogene Proteins c-kit - antagonists & inhibitors ; Proto-Oncogene Proteins c-kit - genetics ; Proto-Oncogene Proteins c-kit - metabolism ; RBPMS2 ; Receptor, Platelet-Derived Growth Factor alpha - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA-binding protein ; RNA-Binding Proteins - biosynthesis ; RNA-Binding Proteins - metabolism ; Signal Transduction ; Smooth muscle cells ; Tissues and Organs</subject><ispartof>Experimental and molecular pathology, 2013-04, Vol.94 (2), p.314-321</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-bda9f6f415462bed1fc5af3854a17814bb4e014ba8d4bfbae9fc8afa69bc3daa3</citedby><cites>FETCH-LOGICAL-c438t-bda9f6f415462bed1fc5af3854a17814bb4e014ba8d4bfbae9fc8afa69bc3daa3</cites><orcidid>0000-0003-0366-4315 ; 0000-0002-8902-8274 ; 0000-0001-9040-2481 ; 0000-0001-8363-1614</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.yexmp.2012.12.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23295309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.umontpellier.fr/hal-02543718$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hapkova, Ilona</creatorcontrib><creatorcontrib>Skarda, Josef</creatorcontrib><creatorcontrib>Rouleau, Caroline</creatorcontrib><creatorcontrib>Thys, An</creatorcontrib><creatorcontrib>Notarnicola, Cécile</creatorcontrib><creatorcontrib>Janikova, Maria</creatorcontrib><creatorcontrib>Bernex, Florence</creatorcontrib><creatorcontrib>Rypka, Miroslav</creatorcontrib><creatorcontrib>Vanderwinden, Jean-Marie</creatorcontrib><creatorcontrib>Faure, Sandrine</creatorcontrib><creatorcontrib>Vesely, Jaroslav</creatorcontrib><creatorcontrib>de Santa Barbara, Pascal</creatorcontrib><title>High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors</title><title>Experimental and molecular pathology</title><addtitle>Exp Mol Pathol</addtitle><description>Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n=23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p<0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Amino Acid Sequence</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Gastrointestinal Neoplasms - genetics</subject><subject>Gastrointestinal Neoplasms - metabolism</subject><subject>Gastrointestinal stromal tumors (GIST)</subject><subject>Gastrointestinal Stromal Tumors - genetics</subject><subject>Gastrointestinal Stromal Tumors - metabolism</subject><subject>Gastrointestinal Tract - metabolism</subject><subject>Gene Expression</subject><subject>HEK293 Cells</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Interstitial cell of Cajal</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Proto-Oncogene Proteins c-kit - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-kit - genetics</subject><subject>Proto-Oncogene Proteins c-kit - metabolism</subject><subject>RBPMS2</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA-binding protein</subject><subject>RNA-Binding Proteins - biosynthesis</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Signal Transduction</subject><subject>Smooth muscle cells</subject><subject>Tissues and Organs</subject><issn>0014-4800</issn><issn>1096-0945</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtPwzAMgCMEgvH4BUioRzh0OE1a2gOHgYAhjYd4nKMkdbZMbTOSDsG_J2PAEcmSk-izHX-EHFIYUqDF6Xz4iR_tYpgBzYYxAPgGGVCoihQqnm-SAQDlKS8BdshuCHMAqCK7TXYyllU5g2pAXsZ2OkvwY-ExBOu6xJmkn2HydD9Kle1q202ThXc92i55uni8e86SeJrK0Htnux5DbzvZJKtrG3O_bJ0P-2TLyCbgwU_eI6_XVy-X43TycHN7OZqkmrOyT1UtK1MYTnNeZApranQuDStzLulZSblSHOMGSpY1V0ZJrIwupZFFpTSrpWR75GTddyYbsfC2lf5TOGnFeDQRqzfIcs7OaPlOI3u8ZuM2b8v4b9HaoLFpZIduGQRlcWYODCCibI1q70LwaP56UxAr9WIuvtWLlXoRI6qPVUc_A5aqxfqv5td1BM7XAEYl7xa9CNpip7G2HnUvamf_HfAFWXOWnw</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Hapkova, Ilona</creator><creator>Skarda, Josef</creator><creator>Rouleau, Caroline</creator><creator>Thys, An</creator><creator>Notarnicola, Cécile</creator><creator>Janikova, Maria</creator><creator>Bernex, Florence</creator><creator>Rypka, Miroslav</creator><creator>Vanderwinden, Jean-Marie</creator><creator>Faure, Sandrine</creator><creator>Vesely, Jaroslav</creator><creator>de Santa Barbara, Pascal</creator><general>Elsevier Inc</general><general>Elsevier</general><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>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-0366-4315</orcidid><orcidid>https://orcid.org/0000-0002-8902-8274</orcidid><orcidid>https://orcid.org/0000-0001-9040-2481</orcidid><orcidid>https://orcid.org/0000-0001-8363-1614</orcidid></search><sort><creationdate>20130401</creationdate><title>High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors</title><author>Hapkova, Ilona ; Skarda, Josef ; Rouleau, Caroline ; Thys, An ; Notarnicola, Cécile ; Janikova, Maria ; Bernex, Florence ; Rypka, Miroslav ; Vanderwinden, Jean-Marie ; Faure, Sandrine ; Vesely, Jaroslav ; de Santa Barbara, Pascal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-bda9f6f415462bed1fc5af3854a17814bb4e014ba8d4bfbae9fc8afa69bc3daa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Amino Acid Sequence</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Gastrointestinal Neoplasms - genetics</topic><topic>Gastrointestinal Neoplasms - metabolism</topic><topic>Gastrointestinal stromal tumors (GIST)</topic><topic>Gastrointestinal Stromal Tumors - genetics</topic><topic>Gastrointestinal Stromal Tumors - metabolism</topic><topic>Gastrointestinal Tract - metabolism</topic><topic>Gene Expression</topic><topic>HEK293 Cells</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Interstitial cell of Cajal</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Proto-Oncogene Proteins c-kit - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-kit - genetics</topic><topic>Proto-Oncogene Proteins c-kit - metabolism</topic><topic>RBPMS2</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA-binding protein</topic><topic>RNA-Binding Proteins - biosynthesis</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Signal Transduction</topic><topic>Smooth muscle cells</topic><topic>Tissues and Organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hapkova, Ilona</creatorcontrib><creatorcontrib>Skarda, Josef</creatorcontrib><creatorcontrib>Rouleau, Caroline</creatorcontrib><creatorcontrib>Thys, An</creatorcontrib><creatorcontrib>Notarnicola, Cécile</creatorcontrib><creatorcontrib>Janikova, Maria</creatorcontrib><creatorcontrib>Bernex, Florence</creatorcontrib><creatorcontrib>Rypka, Miroslav</creatorcontrib><creatorcontrib>Vanderwinden, Jean-Marie</creatorcontrib><creatorcontrib>Faure, Sandrine</creatorcontrib><creatorcontrib>Vesely, Jaroslav</creatorcontrib><creatorcontrib>de Santa Barbara, Pascal</creatorcontrib><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>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Experimental and molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hapkova, Ilona</au><au>Skarda, Josef</au><au>Rouleau, Caroline</au><au>Thys, An</au><au>Notarnicola, Cécile</au><au>Janikova, Maria</au><au>Bernex, Florence</au><au>Rypka, Miroslav</au><au>Vanderwinden, Jean-Marie</au><au>Faure, Sandrine</au><au>Vesely, Jaroslav</au><au>de Santa Barbara, Pascal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors</atitle><jtitle>Experimental and molecular pathology</jtitle><addtitle>Exp Mol Pathol</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>94</volume><issue>2</issue><spage>314</spage><epage>321</epage><pages>314-321</pages><issn>0014-4800</issn><eissn>1096-0945</eissn><abstract>Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n=23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p<0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>23295309</pmid><doi>10.1016/j.yexmp.2012.12.004</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0366-4315</orcidid><orcidid>https://orcid.org/0000-0002-8902-8274</orcidid><orcidid>https://orcid.org/0000-0001-9040-2481</orcidid><orcidid>https://orcid.org/0000-0001-8363-1614</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Experimental and molecular pathology, 2013-04, Vol.94 (2), p.314-321 |
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| subjects | Adult Aged Amino Acid Sequence Cell Line, Tumor Female Gastrointestinal Neoplasms - genetics Gastrointestinal Neoplasms - metabolism Gastrointestinal stromal tumors (GIST) Gastrointestinal Stromal Tumors - genetics Gastrointestinal Stromal Tumors - metabolism Gastrointestinal Tract - metabolism Gene Expression HEK293 Cells Human health and pathology Humans Interstitial cell of Cajal Life Sciences Male Middle Aged Molecular Sequence Data Mutation Proto-Oncogene Proteins c-kit - antagonists & inhibitors Proto-Oncogene Proteins c-kit - genetics Proto-Oncogene Proteins c-kit - metabolism RBPMS2 Receptor, Platelet-Derived Growth Factor alpha - genetics RNA, Messenger - genetics RNA, Messenger - metabolism RNA-binding protein RNA-Binding Proteins - biosynthesis RNA-Binding Proteins - metabolism Signal Transduction Smooth muscle cells Tissues and Organs |
| title | High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors |
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