Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome
A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evo...
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| Veröffentlicht in: | Oncogene 2011-08, Vol.30 (33), p.3585-3598 |
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| creator | Pal, J Bertheau, R Buon, L Qazi, A Batchu, R B Bandyopadhyay, S Ali-Fehmi, R Beer, D G Weaver, D W Shmookler Reis, R J Goyal, R K Huang, Q Munshi, N C Shammas, M A |
| description | A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (
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| doi_str_mv | 10.1038/onc.2011.83 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3406293</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A266563739</galeid><sourcerecordid>A266563739</sourcerecordid><originalsourceid>FETCH-LOGICAL-c602t-f4e36af0cab06168c7fde8e832b0f837679076b20780621b380eef3180a74ab93</originalsourceid><addsrcrecordid>eNp9kl9r1EAUxYMotlaffJdBkQp21_m3k4kPwlq1CgVB9HmYTG52pyQz7Uyy4MfwG3vjrl0rVfIQmPu7595zOUXxmNE5o0K_isHNOWVsrsWd4pDJUs0Wi0reLQ5ptaCzigt-UDzI-YJSWlaU3y8OOJP4yvRh8eMMQuy9I7CJ3Tj4GIgP5K1NCYbhOBPbYN3Z5DxiljjouvyauOQH72xHUuwgk9gS6GBjB2jIOn9ZvluwE7KOfeziKo6ZJHCxr32wv_RtaMiyG0mGqxGCw36cOKyBrKZV4GFxr7Vdhke7_1Hx7cP7r6cfZ-efzz6dLs9nTlE-zFoJQtmWOltTxZR2ZduABi14TVstSoVWS1VzWmqqOKuFpgCtYJraUtq6EkfFm63u5Vj30DgIQ7KduUy-t-m7idabm5Xg12YVN0ZIFKwEChzvBFJEJ3kwvc_TgWwAdG20lpJzLadRL_5LMkoRXiihEX36F3oRxxTwEKinGVrXDKFn_4K4kkzSkjGxp1a2A-NDG9GGmyabJVcKx5Vi2m1-C4VfAxiLGKD1-H6j4eW2waWYc4L2-mSMmimQBgNppkAaPS3x5M8rX7O_E4jA8x1gMyaqTTY4n_eclKoSXCJ3suUylsIK0t7zbXN_AiJk9lg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2641407113</pqid></control><display><type>article</type><title>Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome</title><source>MEDLINE</source><source>Nature</source><source>EZB-FREE-00999 freely available EZB journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>Pal, J ; Bertheau, R ; Buon, L ; Qazi, A ; Batchu, R B ; Bandyopadhyay, S ; Ali-Fehmi, R ; Beer, D G ; Weaver, D W ; Shmookler Reis, R J ; Goyal, R K ; Huang, Q ; Munshi, N C ; Shammas, M A</creator><creatorcontrib>Pal, J ; Bertheau, R ; Buon, L ; Qazi, A ; Batchu, R B ; Bandyopadhyay, S ; Ali-Fehmi, R ; Beer, D G ; Weaver, D W ; Shmookler Reis, R J ; Goyal, R K ; Huang, Q ; Munshi, N C ; Shammas, M A</creatorcontrib><description>A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (
P
<0.02) in several independent experiments employing single-nucleotide polymorphism arrays. The reduction in copy-number changes, following shRNA treatment, was confirmed by Comparative Genome Hybridization analyses of the same DNA samples. Moreover, the chromosomal distributions of mutations correlated strongly with frequencies and locations of Alu interspersed repetitive elements on individual chromosomes. We conclude that the hsRAD51 protein level is systematically elevated in BAC, contributes significantly to genomic evolution during serial propagation of these cells and correlates with disease progression. Alu sequences may serve as substrates for elevated HR during cell proliferation
in vitro
, as they have been reported to do during the evolution of species, and thus may provide additional targets for prevention or treatment of this disease.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2011.83</identifier><identifier>PMID: 21423218</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/212/2304 ; 631/337/1427/2190 ; 692/699/67/1504/1477 ; Adenocarcinoma ; Adenocarcinoma - genetics ; Alu Elements ; Apoptosis ; Bacterial artificial chromosomes ; Barrett Esophagus - genetics ; Biological and medical sciences ; Cancer ; Cell Biology ; Cell Line, Tumor ; Cell physiology ; Cell proliferation ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cellular biology ; Chromosomes ; Copy number ; Diverse techniques ; DNA ; Esophageal Neoplasms - genetics ; Esophagus ; Evolution ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genetic aspects ; Genetic recombination ; Genic rearrangement. Recombination. Transposable element ; Genome, Human ; Genomes ; Genomic instability ; Genomics ; Head & neck cancer ; Heterozygosity ; Homologous recombination ; Human Genetics ; Humans ; Hybridization ; Hybridization analysis ; Internal Medicine ; Loss of Heterozygosity ; Medicine ; Medicine & Public Health ; Molecular and cellular biology ; Molecular genetics ; Mutation ; Oncology ; original-article ; Rad51 Recombinase - physiology ; Recombinase ; Recombination, Genetic ; Risk factors ; RNA ; Single-nucleotide polymorphism</subject><ispartof>Oncogene, 2011-08, Vol.30 (33), p.3585-3598</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2011.</rights><rights>Copyright Nature Publishing Group Aug 18, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c602t-f4e36af0cab06168c7fde8e832b0f837679076b20780621b380eef3180a74ab93</citedby><cites>FETCH-LOGICAL-c602t-f4e36af0cab06168c7fde8e832b0f837679076b20780621b380eef3180a74ab93</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/onc.2011.83$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2011.83$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24469324$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21423218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pal, J</creatorcontrib><creatorcontrib>Bertheau, R</creatorcontrib><creatorcontrib>Buon, L</creatorcontrib><creatorcontrib>Qazi, A</creatorcontrib><creatorcontrib>Batchu, R B</creatorcontrib><creatorcontrib>Bandyopadhyay, S</creatorcontrib><creatorcontrib>Ali-Fehmi, R</creatorcontrib><creatorcontrib>Beer, D G</creatorcontrib><creatorcontrib>Weaver, D W</creatorcontrib><creatorcontrib>Shmookler Reis, R J</creatorcontrib><creatorcontrib>Goyal, R K</creatorcontrib><creatorcontrib>Huang, Q</creatorcontrib><creatorcontrib>Munshi, N C</creatorcontrib><creatorcontrib>Shammas, M A</creatorcontrib><title>Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (
P
<0.02) in several independent experiments employing single-nucleotide polymorphism arrays. The reduction in copy-number changes, following shRNA treatment, was confirmed by Comparative Genome Hybridization analyses of the same DNA samples. Moreover, the chromosomal distributions of mutations correlated strongly with frequencies and locations of Alu interspersed repetitive elements on individual chromosomes. We conclude that the hsRAD51 protein level is systematically elevated in BAC, contributes significantly to genomic evolution during serial propagation of these cells and correlates with disease progression. Alu sequences may serve as substrates for elevated HR during cell proliferation
in vitro
, as they have been reported to do during the evolution of species, and thus may provide additional targets for prevention or treatment of this disease.</description><subject>631/208/212/2304</subject><subject>631/337/1427/2190</subject><subject>692/699/67/1504/1477</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Alu Elements</subject><subject>Apoptosis</subject><subject>Bacterial artificial chromosomes</subject><subject>Barrett Esophagus - genetics</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cell Biology</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>Cellular biology</subject><subject>Chromosomes</subject><subject>Copy number</subject><subject>Diverse techniques</subject><subject>DNA</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophagus</subject><subject>Evolution</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic recombination</subject><subject>Genic rearrangement. Recombination. Transposable element</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Genomic instability</subject><subject>Genomics</subject><subject>Head & neck cancer</subject><subject>Heterozygosity</subject><subject>Homologous recombination</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Hybridization analysis</subject><subject>Internal Medicine</subject><subject>Loss of Heterozygosity</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Mutation</subject><subject>Oncology</subject><subject>original-article</subject><subject>Rad51 Recombinase - physiology</subject><subject>Recombinase</subject><subject>Recombination, Genetic</subject><subject>Risk factors</subject><subject>RNA</subject><subject>Single-nucleotide polymorphism</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kl9r1EAUxYMotlaffJdBkQp21_m3k4kPwlq1CgVB9HmYTG52pyQz7Uyy4MfwG3vjrl0rVfIQmPu7595zOUXxmNE5o0K_isHNOWVsrsWd4pDJUs0Wi0reLQ5ptaCzigt-UDzI-YJSWlaU3y8OOJP4yvRh8eMMQuy9I7CJ3Tj4GIgP5K1NCYbhOBPbYN3Z5DxiljjouvyauOQH72xHUuwgk9gS6GBjB2jIOn9ZvluwE7KOfeziKo6ZJHCxr32wv_RtaMiyG0mGqxGCw36cOKyBrKZV4GFxr7Vdhke7_1Hx7cP7r6cfZ-efzz6dLs9nTlE-zFoJQtmWOltTxZR2ZduABi14TVstSoVWS1VzWmqqOKuFpgCtYJraUtq6EkfFm63u5Vj30DgIQ7KduUy-t-m7idabm5Xg12YVN0ZIFKwEChzvBFJEJ3kwvc_TgWwAdG20lpJzLadRL_5LMkoRXiihEX36F3oRxxTwEKinGVrXDKFn_4K4kkzSkjGxp1a2A-NDG9GGmyabJVcKx5Vi2m1-C4VfAxiLGKD1-H6j4eW2waWYc4L2-mSMmimQBgNppkAaPS3x5M8rX7O_E4jA8x1gMyaqTTY4n_eclKoSXCJ3suUylsIK0t7zbXN_AiJk9lg</recordid><startdate>20110818</startdate><enddate>20110818</enddate><creator>Pal, J</creator><creator>Bertheau, R</creator><creator>Buon, L</creator><creator>Qazi, A</creator><creator>Batchu, R B</creator><creator>Bandyopadhyay, S</creator><creator>Ali-Fehmi, R</creator><creator>Beer, D G</creator><creator>Weaver, D W</creator><creator>Shmookler Reis, R J</creator><creator>Goyal, R K</creator><creator>Huang, Q</creator><creator>Munshi, N C</creator><creator>Shammas, M A</creator><general>Nature Publishing Group UK</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>20110818</creationdate><title>Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome</title><author>Pal, J ; Bertheau, R ; Buon, L ; Qazi, A ; Batchu, R B ; Bandyopadhyay, S ; Ali-Fehmi, R ; Beer, D G ; Weaver, D W ; Shmookler Reis, R J ; Goyal, R K ; Huang, Q ; Munshi, N C ; Shammas, M A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c602t-f4e36af0cab06168c7fde8e832b0f837679076b20780621b380eef3180a74ab93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/208/212/2304</topic><topic>631/337/1427/2190</topic><topic>692/699/67/1504/1477</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - genetics</topic><topic>Alu Elements</topic><topic>Apoptosis</topic><topic>Bacterial artificial chromosomes</topic><topic>Barrett Esophagus - genetics</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cell Biology</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>Cellular biology</topic><topic>Chromosomes</topic><topic>Copy number</topic><topic>Diverse techniques</topic><topic>DNA</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophagus</topic><topic>Evolution</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genetic recombination</topic><topic>Genic rearrangement. Recombination. Transposable element</topic><topic>Genome, Human</topic><topic>Genomes</topic><topic>Genomic instability</topic><topic>Genomics</topic><topic>Head & neck cancer</topic><topic>Heterozygosity</topic><topic>Homologous recombination</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Hybridization analysis</topic><topic>Internal Medicine</topic><topic>Loss of Heterozygosity</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Mutation</topic><topic>Oncology</topic><topic>original-article</topic><topic>Rad51 Recombinase - physiology</topic><topic>Recombinase</topic><topic>Recombination, Genetic</topic><topic>Risk factors</topic><topic>RNA</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pal, J</creatorcontrib><creatorcontrib>Bertheau, R</creatorcontrib><creatorcontrib>Buon, L</creatorcontrib><creatorcontrib>Qazi, A</creatorcontrib><creatorcontrib>Batchu, R B</creatorcontrib><creatorcontrib>Bandyopadhyay, S</creatorcontrib><creatorcontrib>Ali-Fehmi, R</creatorcontrib><creatorcontrib>Beer, D G</creatorcontrib><creatorcontrib>Weaver, D W</creatorcontrib><creatorcontrib>Shmookler Reis, R J</creatorcontrib><creatorcontrib>Goyal, R K</creatorcontrib><creatorcontrib>Huang, Q</creatorcontrib><creatorcontrib>Munshi, N C</creatorcontrib><creatorcontrib>Shammas, M A</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>ProQuest Health and Medical</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>ProQuest Research Library</collection><collection>ProQuest Biological Science Journals</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>Pal, J</au><au>Bertheau, R</au><au>Buon, L</au><au>Qazi, A</au><au>Batchu, R B</au><au>Bandyopadhyay, S</au><au>Ali-Fehmi, R</au><au>Beer, D G</au><au>Weaver, D W</au><au>Shmookler Reis, R J</au><au>Goyal, R K</au><au>Huang, Q</au><au>Munshi, N C</au><au>Shammas, M A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2011-08-18</date><risdate>2011</risdate><volume>30</volume><issue>33</issue><spage>3585</spage><epage>3598</epage><pages>3585-3598</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (
P
<0.02) in several independent experiments employing single-nucleotide polymorphism arrays. The reduction in copy-number changes, following shRNA treatment, was confirmed by Comparative Genome Hybridization analyses of the same DNA samples. Moreover, the chromosomal distributions of mutations correlated strongly with frequencies and locations of Alu interspersed repetitive elements on individual chromosomes. We conclude that the hsRAD51 protein level is systematically elevated in BAC, contributes significantly to genomic evolution during serial propagation of these cells and correlates with disease progression. Alu sequences may serve as substrates for elevated HR during cell proliferation
in vitro
, as they have been reported to do during the evolution of species, and thus may provide additional targets for prevention or treatment of this disease.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21423218</pmid><doi>10.1038/onc.2011.83</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncogene, 2011-08, Vol.30 (33), p.3585-3598 |
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| subjects | 631/208/212/2304 631/337/1427/2190 692/699/67/1504/1477 Adenocarcinoma Adenocarcinoma - genetics Alu Elements Apoptosis Bacterial artificial chromosomes Barrett Esophagus - genetics Biological and medical sciences Cancer Cell Biology Cell Line, Tumor Cell physiology Cell proliferation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cellular biology Chromosomes Copy number Diverse techniques DNA Esophageal Neoplasms - genetics Esophagus Evolution Fundamental and applied biological sciences. Psychology Gene expression Genetic aspects Genetic recombination Genic rearrangement. Recombination. Transposable element Genome, Human Genomes Genomic instability Genomics Head & neck cancer Heterozygosity Homologous recombination Human Genetics Humans Hybridization Hybridization analysis Internal Medicine Loss of Heterozygosity Medicine Medicine & Public Health Molecular and cellular biology Molecular genetics Mutation Oncology original-article Rad51 Recombinase - physiology Recombinase Recombination, Genetic Risk factors RNA Single-nucleotide polymorphism |
| title | Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T21%3A46%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genomic%20evolution%20in%20Barrett's%20adenocarcinoma%20cells:%20critical%20roles%20of%20elevated%20hsRAD51,%20homologous%20recombination%20and%20Alu%20sequences%20in%20the%20genome&rft.jtitle=Oncogene&rft.au=Pal,%20J&rft.date=2011-08-18&rft.volume=30&rft.issue=33&rft.spage=3585&rft.epage=3598&rft.pages=3585-3598&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/onc.2011.83&rft_dat=%3Cgale_pubme%3EA266563739%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2641407113&rft_id=info:pmid/21423218&rft_galeid=A266563739&rfr_iscdi=true |