EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53
The enhancer of zeste homolog 2 (EZH2) methyltransferase is a transcriptional repressor. EZH2 is abnormally elevated in epithelial ovarian cancer (EOC). We demonstrated that EZH2 knockdown inhibited cell growth, activated apoptosis, and enhanced chemosensitivity. Further, silencing of EZH2 resulted...
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Veröffentlicht in: | Cancer letters 2013-08, Vol.336 (1), p.53-60 |
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creator | Seward, Shelly Semaan, Assaad Qazi, Aamer M Gruzdyn, Oksana V Chamala, Sreedhar Bryant, Christopher C Kumar, Sanjeev Cameron, David Sethi, Seema Ali-Fehmi, Rouba Morris, Robert Bouwman, David L Munkarah, Adnan R Weaver, Donald W Gruber, Scott A Batchu, Ramesh B |
description | The enhancer of zeste homolog 2 (EZH2) methyltransferase is a transcriptional repressor. EZH2 is abnormally elevated in epithelial ovarian cancer (EOC). We demonstrated that EZH2 knockdown inhibited cell growth, activated apoptosis, and enhanced chemosensitivity. Further, silencing of EZH2 resulted in re-expression of p21(waf1/cip1) and down-regulation of mutant p53. Finally, EZH2 knockdown contributed to attenuated EOC growth in SCID mice. |
doi_str_mv | 10.1016/j.canlet.2013.04.012 |
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EZH2 is abnormally elevated in epithelial ovarian cancer (EOC). We demonstrated that EZH2 knockdown inhibited cell growth, activated apoptosis, and enhanced chemosensitivity. Further, silencing of EZH2 resulted in re-expression of p21(waf1/cip1) and down-regulation of mutant p53. Finally, EZH2 knockdown contributed to attenuated EOC growth in SCID mice.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>Enhancer of Zeste Homolog 2 Protein</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Mutation</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Transplantation</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Polycomb Repressive Complex 2 - genetics</subject><subject>Polycomb Repressive Complex 2 - metabolism</subject><subject>RNA Interference</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kMtKAzEUQIMgtj7-QCTLupgxmUxeyyK-QBREN25KJnOjqdPMmKTW_oWfbIt1dblwzrlwETqlpKSEiot5aU3oIJcVoawkdUlotYfGVMmqkFqRETpMaU4I4bXkB2hUMUEY52qMfq5ebyvcdL39MC3gZo2fHqbYhwzRQYRgYbO8-8bnhN9iv8rvuHe4_zLRm4A3Vy3EreWM9Z3PJvvwhiMU8D1ESMn3YcsPFZ2sjKMX1g_0HJvQbp1deGssltmEjAfOjtG-M12Ck908Qi_XV8-Xt8X9483d5fS-2LRoLhopnRakbXmtqWs0oZRxoZQkUnEJULdgtdGUWSkY1bp2gjdMa2mJAnA1O0KTv-4Q-88lpDxb-GSh60yAfplmlAmplKiE2KBnO3TZLKCdDdEvTFzP_r_IfgFedXPP</recordid><startdate>20130809</startdate><enddate>20130809</enddate><creator>Seward, Shelly</creator><creator>Semaan, Assaad</creator><creator>Qazi, Aamer M</creator><creator>Gruzdyn, Oksana V</creator><creator>Chamala, Sreedhar</creator><creator>Bryant, Christopher C</creator><creator>Kumar, Sanjeev</creator><creator>Cameron, David</creator><creator>Sethi, Seema</creator><creator>Ali-Fehmi, Rouba</creator><creator>Morris, Robert</creator><creator>Bouwman, David L</creator><creator>Munkarah, Adnan R</creator><creator>Weaver, Donald W</creator><creator>Gruber, Scott A</creator><creator>Batchu, Ramesh B</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20130809</creationdate><title>EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53</title><author>Seward, Shelly ; Semaan, Assaad ; Qazi, Aamer M ; Gruzdyn, Oksana V ; Chamala, Sreedhar ; Bryant, Christopher C ; Kumar, Sanjeev ; Cameron, David ; Sethi, Seema ; Ali-Fehmi, Rouba ; Morris, Robert ; Bouwman, David L ; Munkarah, Adnan R ; Weaver, Donald W ; Gruber, Scott A ; Batchu, Ramesh B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-b77f960dd5491fb901135688707857ee4dec9a913c7631994f65b3997c08eef43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>Enhancer of Zeste Homolog 2 Protein</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Mutation</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasm Transplantation</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Polycomb Repressive Complex 2 - genetics</topic><topic>Polycomb Repressive Complex 2 - metabolism</topic><topic>RNA Interference</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seward, Shelly</creatorcontrib><creatorcontrib>Semaan, Assaad</creatorcontrib><creatorcontrib>Qazi, Aamer M</creatorcontrib><creatorcontrib>Gruzdyn, Oksana V</creatorcontrib><creatorcontrib>Chamala, Sreedhar</creatorcontrib><creatorcontrib>Bryant, Christopher C</creatorcontrib><creatorcontrib>Kumar, Sanjeev</creatorcontrib><creatorcontrib>Cameron, David</creatorcontrib><creatorcontrib>Sethi, Seema</creatorcontrib><creatorcontrib>Ali-Fehmi, Rouba</creatorcontrib><creatorcontrib>Morris, Robert</creatorcontrib><creatorcontrib>Bouwman, David L</creatorcontrib><creatorcontrib>Munkarah, Adnan R</creatorcontrib><creatorcontrib>Weaver, Donald W</creatorcontrib><creatorcontrib>Gruber, Scott A</creatorcontrib><creatorcontrib>Batchu, Ramesh B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seward, Shelly</au><au>Semaan, Assaad</au><au>Qazi, Aamer M</au><au>Gruzdyn, Oksana V</au><au>Chamala, Sreedhar</au><au>Bryant, Christopher C</au><au>Kumar, Sanjeev</au><au>Cameron, David</au><au>Sethi, Seema</au><au>Ali-Fehmi, Rouba</au><au>Morris, Robert</au><au>Bouwman, David L</au><au>Munkarah, Adnan R</au><au>Weaver, Donald W</au><au>Gruber, Scott A</au><au>Batchu, Ramesh B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2013-08-09</date><risdate>2013</risdate><volume>336</volume><issue>1</issue><spage>53</spage><epage>60</epage><pages>53-60</pages><eissn>1872-7980</eissn><abstract>The enhancer of zeste homolog 2 (EZH2) methyltransferase is a transcriptional repressor. 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subjects | Animals Apoptosis Cell Line, Tumor Cell Proliferation Cyclin-Dependent Kinase Inhibitor p21 - genetics Cyclin-Dependent Kinase Inhibitor p21 - metabolism Enhancer of Zeste Homolog 2 Protein Female Gene Expression Regulation, Neoplastic Humans Mice Mice, SCID Mutation Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Transplantation Oligonucleotide Array Sequence Analysis Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Polycomb Repressive Complex 2 - genetics Polycomb Repressive Complex 2 - metabolism RNA Interference Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism |
title | EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53 |
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