Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro
Polypyrimidine tract-binding protein (PTB) is an RNA-binding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) stain...
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| Veröffentlicht in: | Oncogene 2007-07, Vol.26 (34), p.4961-4968 |
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| creator | He, X Pool, M Darcy, K M Lim, S B Auersperg, N Coon, J S Beck, W T |
| description | Polypyrimidine tract-binding protein (PTB) is an RNA-binding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matched-normal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and
in vitro
invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer. |
| doi_str_mv | 10.1038/sj.onc.1210307 |
| format | Article |
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in vitro
invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1210307</identifier><identifier>PMID: 17310993</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Apoptosis ; Biological and medical sciences ; Cell Biology ; Cell growth ; Cell Line, Tumor ; Cell physiology ; Cell Proliferation ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; DNA binding proteins ; Doxycycline ; Epithelial cells ; Female ; Female genital diseases ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genetic aspects ; Genetics ; Gynecology. Andrology. Obstetrics ; Health aspects ; Human Genetics ; Humans ; Immunoblotting ; Immunohistochemistry ; Internal Medicine ; Invasiveness ; Medical sciences ; Medicine ; Medicine & Public Health ; Molecular and cellular biology ; Neoplasm Invasiveness ; Oncology ; original-article ; Ovarian cancer ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Ovarian tumors ; Physiological aspects ; Polypyrimidine tract-binding protein ; Polypyrimidine Tract-Binding Protein - antagonists & inhibitors ; Polypyrimidine Tract-Binding Protein - metabolism ; Proteins ; Ribonucleic acid ; RNA ; RNA Interference ; RNA processing ; RNA splicing ; RNA-binding protein ; Simian virus 40 ; siRNA ; Therapeutic targets ; Tissue Array Analysis ; Tumorigenesis ; Tumors ; Western blotting</subject><ispartof>Oncogene, 2007-07, Vol.26 (34), p.4961-4968</ispartof><rights>Springer Nature Limited 2007</rights><rights>2007 INIST-CNRS</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 26, 2007</rights><rights>Nature Publishing Group 2007.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c708t-a13fcc38dc0cdadccd2082134d3e3aeb2a64ef732500294b27c65547bd5a64913</citedby><cites>FETCH-LOGICAL-c708t-a13fcc38dc0cdadccd2082134d3e3aeb2a64ef732500294b27c65547bd5a64913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1210307$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1210307$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18955822$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17310993$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, X</creatorcontrib><creatorcontrib>Pool, M</creatorcontrib><creatorcontrib>Darcy, K M</creatorcontrib><creatorcontrib>Lim, S B</creatorcontrib><creatorcontrib>Auersperg, N</creatorcontrib><creatorcontrib>Coon, J S</creatorcontrib><creatorcontrib>Beck, W T</creatorcontrib><title>Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Polypyrimidine tract-binding protein (PTB) is an RNA-binding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matched-normal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and
in vitro
invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.</description><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell Biology</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell physiology</subject><subject>Cell Proliferation</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>DNA binding proteins</subject><subject>Doxycycline</subject><subject>Epithelial cells</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunohistochemistry</subject><subject>Internal Medicine</subject><subject>Invasiveness</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular and cellular biology</subject><subject>Neoplasm Invasiveness</subject><subject>Oncology</subject><subject>original-article</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovarian tumors</subject><subject>Physiological aspects</subject><subject>Polypyrimidine tract-binding protein</subject><subject>Polypyrimidine Tract-Binding Protein - antagonists & inhibitors</subject><subject>Polypyrimidine Tract-Binding Protein - metabolism</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA processing</subject><subject>RNA splicing</subject><subject>RNA-binding protein</subject><subject>Simian virus 40</subject><subject>siRNA</subject><subject>Therapeutic targets</subject><subject>Tissue Array Analysis</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Western blotting</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk1v1DAQhiMEotvClSOyQOWWrT_iOLkgVRVfohIXOFuO7aResnawk1T775moEQuoVeWDNZ7HM_POTJa9InhLMKsu0m4bvN4SChYWT7INKUSZc14XT7MNrjnOa8roSXaa0g5jLGpMn2cnRDCC65ptsuGrD_qnCbcehRYNoT8Mh-j2zjhv0RiVHvPGebA6NMQwWudRmoYh2pRsQmFW0SmPxmkfItK271EXw-14g5Q3yPlZJTdbDzAYaHZjDC-yZ63qk3253mfZj48fvl99zq-_ffpydXmda4GrMVeEtVqzymisjTJaG4orSlhhmGXKNlSVhW0FoxxjWhcNFbrkvBCN4eCpCTvL3t_FHaZmb422HtT0cgBxKh5kUE7-6_HuRnZhlpSVhSAlBHi3Bojh12TTKPcuLRKVt2FKUmBRcGjuoyBUTSpG6KMgqQVjgi61v_0P3IUpemiXpGVBmIBhC6DePEhRwYqSC3wM1aneSufbsAx1ySsvSUUxYaAXqO09FBxj904Hb1sH7_d90DGkFG37p7EEy2UxZdpJWEy5LiZ8eP33OI74uokAnK-ASlr1bVReu3Tkqprzii5NvLjjErh8Z-NR9QOpfwNvJvyP</recordid><startdate>20070726</startdate><enddate>20070726</enddate><creator>He, X</creator><creator>Pool, M</creator><creator>Darcy, K M</creator><creator>Lim, S B</creator><creator>Auersperg, N</creator><creator>Coon, J S</creator><creator>Beck, W T</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070726</creationdate><title>Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro</title><author>He, X ; Pool, M ; Darcy, K M ; Lim, S B ; Auersperg, N ; Coon, J S ; Beck, W T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c708t-a13fcc38dc0cdadccd2082134d3e3aeb2a64ef732500294b27c65547bd5a64913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cell Biology</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell physiology</topic><topic>Cell Proliferation</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>DNA binding proteins</topic><topic>Doxycycline</topic><topic>Epithelial cells</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunohistochemistry</topic><topic>Internal Medicine</topic><topic>Invasiveness</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular and cellular biology</topic><topic>Neoplasm Invasiveness</topic><topic>Oncology</topic><topic>original-article</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovarian tumors</topic><topic>Physiological aspects</topic><topic>Polypyrimidine tract-binding protein</topic><topic>Polypyrimidine Tract-Binding Protein - antagonists & inhibitors</topic><topic>Polypyrimidine Tract-Binding Protein - metabolism</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA processing</topic><topic>RNA splicing</topic><topic>RNA-binding protein</topic><topic>Simian virus 40</topic><topic>siRNA</topic><topic>Therapeutic targets</topic><topic>Tissue Array Analysis</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, X</creatorcontrib><creatorcontrib>Pool, M</creatorcontrib><creatorcontrib>Darcy, K M</creatorcontrib><creatorcontrib>Lim, S B</creatorcontrib><creatorcontrib>Auersperg, N</creatorcontrib><creatorcontrib>Coon, J S</creatorcontrib><creatorcontrib>Beck, W T</creatorcontrib><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>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, X</au><au>Pool, M</au><au>Darcy, K M</au><au>Lim, S B</au><au>Auersperg, N</au><au>Coon, J S</au><au>Beck, W T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2007-07-26</date><risdate>2007</risdate><volume>26</volume><issue>34</issue><spage>4961</spage><epage>4968</epage><pages>4961-4968</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Polypyrimidine tract-binding protein (PTB) is an RNA-binding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matched-normal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and
in vitro
invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17310993</pmid><doi>10.1038/sj.onc.1210307</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Apoptosis Biological and medical sciences Cell Biology Cell growth Cell Line, Tumor Cell physiology Cell Proliferation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes DNA binding proteins Doxycycline Epithelial cells Female Female genital diseases Fundamental and applied biological sciences. Psychology Gene expression Genetic aspects Genetics Gynecology. Andrology. Obstetrics Health aspects Human Genetics Humans Immunoblotting Immunohistochemistry Internal Medicine Invasiveness Medical sciences Medicine Medicine & Public Health Molecular and cellular biology Neoplasm Invasiveness Oncology original-article Ovarian cancer Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Ovarian tumors Physiological aspects Polypyrimidine tract-binding protein Polypyrimidine Tract-Binding Protein - antagonists & inhibitors Polypyrimidine Tract-Binding Protein - metabolism Proteins Ribonucleic acid RNA RNA Interference RNA processing RNA splicing RNA-binding protein Simian virus 40 siRNA Therapeutic targets Tissue Array Analysis Tumorigenesis Tumors Western blotting |
| title | Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro |
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