Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells
To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting ∼4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated copy of the K-Ras oncogene. We found that siRNAs ta...
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| Veröffentlicht in: | Molecular cancer therapeutics 2007-01, Vol.6 (1), p.269-276 |
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| container_title | Molecular cancer therapeutics |
| container_volume | 6 |
| creator | Sarthy, Aparna V Morgan-Lappe, Susan E Zakula, Dorothy Vernetti, Lawrence Schurdak, Mark Packer, Jeremy C L Anderson, Mark G Shirasawa, Senji Sasazuki, Takehiko Fesik, Stephen W |
| description | To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library
targeting ∼4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated
copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin)
significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which
the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G 2 -M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These
results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin
protein. [Mol Cancer Ther 2007;6(1):269–76] |
| doi_str_mv | 10.1158/1535-7163.MCT-06-0560 |
| format | Article |
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targeting ∼4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated
copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin)
significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which
the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G 2 -M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These
results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin
protein. [Mol Cancer Ther 2007;6(1):269–76]</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>DOI: 10.1158/1535-7163.MCT-06-0560</identifier><identifier>PMID: 17237286</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Alleles ; Apoptosis ; Cell Death ; Cell Survival ; Cell Transformation, Neoplastic - pathology ; Clone Cells ; G2 Phase ; Genes, Neoplasm ; Genes, ras ; Humans ; Inhibitor of Apoptosis Proteins ; isogenic cancer cell lines ; K-Ras ; Microtubule-Associated Proteins - deficiency ; Microtubule-Associated Proteins - metabolism ; Mitosis ; Mutant Proteins - metabolism ; Neoplasm Proteins - deficiency ; Neoplasm Proteins - metabolism ; Polyploidy ; RNA interference ; RNA, Small Interfering - metabolism ; siRNA ; survivin</subject><ispartof>Molecular cancer therapeutics, 2007-01, Vol.6 (1), p.269-276</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-70027482830c27d72d41cb67191209d5df68546eb5e006e13a5d5a5ebe43e75b3</citedby><cites>FETCH-LOGICAL-c482t-70027482830c27d72d41cb67191209d5df68546eb5e006e13a5d5a5ebe43e75b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3343,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17237286$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sarthy, Aparna V</creatorcontrib><creatorcontrib>Morgan-Lappe, Susan E</creatorcontrib><creatorcontrib>Zakula, Dorothy</creatorcontrib><creatorcontrib>Vernetti, Lawrence</creatorcontrib><creatorcontrib>Schurdak, Mark</creatorcontrib><creatorcontrib>Packer, Jeremy C L</creatorcontrib><creatorcontrib>Anderson, Mark G</creatorcontrib><creatorcontrib>Shirasawa, Senji</creatorcontrib><creatorcontrib>Sasazuki, Takehiko</creatorcontrib><creatorcontrib>Fesik, Stephen W</creatorcontrib><title>Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><description>To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library
targeting ∼4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated
copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin)
significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which
the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G 2 -M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These
results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin
protein. [Mol Cancer Ther 2007;6(1):269–76]</description><subject>Alleles</subject><subject>Apoptosis</subject><subject>Cell Death</subject><subject>Cell Survival</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Clone Cells</subject><subject>G2 Phase</subject><subject>Genes, Neoplasm</subject><subject>Genes, ras</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins</subject><subject>isogenic cancer cell lines</subject><subject>K-Ras</subject><subject>Microtubule-Associated Proteins - deficiency</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Mitosis</subject><subject>Mutant Proteins - metabolism</subject><subject>Neoplasm Proteins - deficiency</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Polyploidy</subject><subject>RNA interference</subject><subject>RNA, Small Interfering - metabolism</subject><subject>siRNA</subject><subject>survivin</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LxDAQhoMofv8EpSdvWSdpk7RHWfzCFcGPk4eQplNb6bZrkir-e1N3waOnvAzPTGYeQk4YzBgT-TkTqaCKyXR2P3-mICkICVtkP9ZzmguWbf_mNbNHDrx_B2B5wdku2WOKp4rncp-8Po3us_1s-6TCVYehHfpk5bBGh31oTdd9Jw6r0aJPQoOJ_6VNlwx1YmyIMWCV3NFH42lwpvf14JaxYrHr_BHZqU3n8XjzHpKXq8vn-Q1dPFzfzi8W1GY5D1QBcBVTnoLlqlK8ypgtpWIF41BUoqplLjKJpUAAiSw1ohJGYIlZikqU6SE5W89dueFjRB_0svXTBqbHYfRaxquLDNS_IAcWHWUQQbEGrRu8jzr0yrVL4741Az3p15NaPanVUb8GqSf9se9088FYRg1_XRvffxs07Vvz1TrU1vQWnUOPxtlGS800l0X6A4L-jsE</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Sarthy, Aparna V</creator><creator>Morgan-Lappe, Susan E</creator><creator>Zakula, Dorothy</creator><creator>Vernetti, Lawrence</creator><creator>Schurdak, Mark</creator><creator>Packer, Jeremy C L</creator><creator>Anderson, Mark G</creator><creator>Shirasawa, Senji</creator><creator>Sasazuki, Takehiko</creator><creator>Fesik, Stephen W</creator><general>American Association for Cancer Research</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20070101</creationdate><title>Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells</title><author>Sarthy, Aparna V ; Morgan-Lappe, Susan E ; Zakula, Dorothy ; Vernetti, Lawrence ; Schurdak, Mark ; Packer, Jeremy C L ; Anderson, Mark G ; Shirasawa, Senji ; Sasazuki, Takehiko ; Fesik, Stephen W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-70027482830c27d72d41cb67191209d5df68546eb5e006e13a5d5a5ebe43e75b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Alleles</topic><topic>Apoptosis</topic><topic>Cell Death</topic><topic>Cell Survival</topic><topic>Cell Transformation, Neoplastic - pathology</topic><topic>Clone Cells</topic><topic>G2 Phase</topic><topic>Genes, Neoplasm</topic><topic>Genes, ras</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins</topic><topic>isogenic cancer cell lines</topic><topic>K-Ras</topic><topic>Microtubule-Associated Proteins - deficiency</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Mitosis</topic><topic>Mutant Proteins - metabolism</topic><topic>Neoplasm Proteins - deficiency</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Polyploidy</topic><topic>RNA interference</topic><topic>RNA, Small Interfering - metabolism</topic><topic>siRNA</topic><topic>survivin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sarthy, Aparna V</creatorcontrib><creatorcontrib>Morgan-Lappe, Susan E</creatorcontrib><creatorcontrib>Zakula, Dorothy</creatorcontrib><creatorcontrib>Vernetti, Lawrence</creatorcontrib><creatorcontrib>Schurdak, Mark</creatorcontrib><creatorcontrib>Packer, Jeremy C L</creatorcontrib><creatorcontrib>Anderson, Mark G</creatorcontrib><creatorcontrib>Shirasawa, Senji</creatorcontrib><creatorcontrib>Sasazuki, Takehiko</creatorcontrib><creatorcontrib>Fesik, Stephen W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sarthy, Aparna V</au><au>Morgan-Lappe, Susan E</au><au>Zakula, Dorothy</au><au>Vernetti, Lawrence</au><au>Schurdak, Mark</au><au>Packer, Jeremy C L</au><au>Anderson, Mark G</au><au>Shirasawa, Senji</au><au>Sasazuki, Takehiko</au><au>Fesik, Stephen W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>6</volume><issue>1</issue><spage>269</spage><epage>276</epage><pages>269-276</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library
targeting ∼4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated
copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin)
significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which
the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G 2 -M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These
results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin
protein. [Mol Cancer Ther 2007;6(1):269–76]</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>17237286</pmid><doi>10.1158/1535-7163.MCT-06-0560</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular cancer therapeutics, 2007-01, Vol.6 (1), p.269-276 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Alleles Apoptosis Cell Death Cell Survival Cell Transformation, Neoplastic - pathology Clone Cells G2 Phase Genes, Neoplasm Genes, ras Humans Inhibitor of Apoptosis Proteins isogenic cancer cell lines K-Ras Microtubule-Associated Proteins - deficiency Microtubule-Associated Proteins - metabolism Mitosis Mutant Proteins - metabolism Neoplasm Proteins - deficiency Neoplasm Proteins - metabolism Polyploidy RNA interference RNA, Small Interfering - metabolism siRNA survivin |
| title | Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells |
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