Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma
Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling...
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| creator | Gibbons, Don L Lin, Wei Creighton, Chad J Zheng, Shuling Berel, Dror Yang, Yanan Raso, Maria Gabriela Liu, Diane D Wistuba, Ignacio I Lozano, Guillermina Kurie, Jonathan M |
| description | Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well understood.
Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-ras(G12D) and p53(R172H). We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
These findings provide evidence that K-ras(G12D); p53(R172H) mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents. |
| doi_str_mv | 10.1371/journal.pone.0005401 |
| format | Article |
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Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-ras(G12D) and p53(R172H). We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
These findings provide evidence that K-ras(G12D); p53(R172H) mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005401</identifier><identifier>PMID: 19404390</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Analysis ; Animals ; Bioinformatics ; Breast cancer ; Cancer ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Biology/Gene Expression ; Cell cycle ; Data mining ; Data processing ; Disease Models, Animal ; Gender differences ; Gene expression ; Gene Expression Profiling ; Genes ; Genes, ras - genetics ; Genetic Predisposition to Disease ; Genetic transcription ; Genetics and Genomics/Gene Expression ; Growth factors ; Health aspects ; Lung cancer ; Lung cancer, Non-small cell ; Lung diseases ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Medical diagnosis ; Medical prognosis ; Metastases ; Metastasis ; Mice ; MicroRNAs ; Mutation ; Mutation, Missense ; Neoplasm Metastasis - genetics ; Non-small cell lung carcinoma ; Oncology ; Oncology/Lung Cancer ; Transcription ; Tumor proteins ; Tumor Suppressor Protein p53 - genetics ; Tumors ; Validation studies</subject><ispartof>PloS one, 2009-04, Vol.4 (4), p.e5401-e5401</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Gibbons et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Gibbons et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c690t-5322f2cfbf628aa62e6d426667f0ba9aed998faa0367f6e7524eaaf7b0e0b3fb3</citedby><cites>FETCH-LOGICAL-c690t-5322f2cfbf628aa62e6d426667f0ba9aed998faa0367f6e7524eaaf7b0e0b3fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671160/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671160/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19404390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Blagosklonny, Mikhail V.</contributor><creatorcontrib>Gibbons, Don L</creatorcontrib><creatorcontrib>Lin, Wei</creatorcontrib><creatorcontrib>Creighton, Chad J</creatorcontrib><creatorcontrib>Zheng, Shuling</creatorcontrib><creatorcontrib>Berel, Dror</creatorcontrib><creatorcontrib>Yang, Yanan</creatorcontrib><creatorcontrib>Raso, Maria Gabriela</creatorcontrib><creatorcontrib>Liu, Diane D</creatorcontrib><creatorcontrib>Wistuba, Ignacio I</creatorcontrib><creatorcontrib>Lozano, Guillermina</creatorcontrib><creatorcontrib>Kurie, Jonathan M</creatorcontrib><title>Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well understood.
Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-ras(G12D) and p53(R172H). We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
These findings provide evidence that K-ras(G12D); p53(R172H) mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Analysis</subject><subject>Animals</subject><subject>Bioinformatics</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Biology/Gene Expression</subject><subject>Cell cycle</subject><subject>Data mining</subject><subject>Data processing</subject><subject>Disease Models, Animal</subject><subject>Gender differences</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Genes, ras - genetics</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic transcription</subject><subject>Genetics and Genomics/Gene Expression</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Lung diseases</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>MicroRNAs</subject><subject>Mutation</subject><subject>Mutation, Missense</subject><subject>Neoplasm Metastasis - genetics</subject><subject>Non-small cell lung carcinoma</subject><subject>Oncology</subject><subject>Oncology/Lung Cancer</subject><subject>Transcription</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumors</subject><subject>Validation studies</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk22L1DAQx4so3nn6DUQLwoEvdk3SbrJ5IxzHqQsHBz69EsI0nXSztMnapHL37U3dqlu5FxLIw-Q3_ySTmSx7TsmSFoK-2fmhd9Au997hkhCyKgl9kJ1SWbAFZ6R4eDQ_yZ6EsEtMseb8cXZCZUnKQpLT7NvV7b7HEKx3ebCNgzikZe5N3mGEECFanWvYg7bxLrcuh7xBh6O180PA1NfYjnw7uCaHGp3X0GvrfAdPs0cG2oDPpvEs-_Lu6vPlh8X1zfvN5cX1QnNJ4mJVMGaYNpXhbA3AGfK6ZJxzYUgFErCWcm0ASJEsHMWKlQhgREWQVIWpirPs5UF33_qgpsAERZkkJS9XXCRicyBqDzu1720H_Z3yYNUvg-8bBX16VIuqKoQxNQMumCwlrCRhQjCiWSVqJiVLWm-n04aqw1qjiz20M9H5jrNb1fgfinFBKSdJ4HwS6P33AUNUnQ0a2xYcppiqhK1JyWQCX_0D3v-2iWogXd8649OpepRUF6Uo6FowOt56eQ-VWo2d1SmHjE32mcPrmUNiIt7GBoYQ1ObTx_9nb77O2fMjdovQxm3w7RBTCoY5WB5A3fsQejR_QkyJGkvgdzTUWAJqKoHk9uL4e_46TTlf_ASvaQGo</recordid><startdate>20090430</startdate><enddate>20090430</enddate><creator>Gibbons, Don L</creator><creator>Lin, Wei</creator><creator>Creighton, Chad J</creator><creator>Zheng, Shuling</creator><creator>Berel, Dror</creator><creator>Yang, Yanan</creator><creator>Raso, Maria Gabriela</creator><creator>Liu, Diane D</creator><creator>Wistuba, Ignacio I</creator><creator>Lozano, Guillermina</creator><creator>Kurie, Jonathan M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090430</creationdate><title>Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma</title><author>Gibbons, Don L ; Lin, Wei ; Creighton, Chad J ; Zheng, Shuling ; Berel, Dror ; Yang, Yanan ; Raso, Maria Gabriela ; Liu, Diane D ; Wistuba, Ignacio I ; Lozano, Guillermina ; Kurie, Jonathan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c690t-5322f2cfbf628aa62e6d426667f0ba9aed998faa0367f6e7524eaaf7b0e0b3fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - 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The biologic basis for NSCLC metastasis is not well understood.
Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-ras(G12D) and p53(R172H). We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature.
These findings provide evidence that K-ras(G12D); p53(R172H) mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19404390</pmid><doi>10.1371/journal.pone.0005401</doi><tpages>e5401</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - pathology Analysis Animals Bioinformatics Breast cancer Cancer Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology Cell Biology/Gene Expression Cell cycle Data mining Data processing Disease Models, Animal Gender differences Gene expression Gene Expression Profiling Genes Genes, ras - genetics Genetic Predisposition to Disease Genetic transcription Genetics and Genomics/Gene Expression Growth factors Health aspects Lung cancer Lung cancer, Non-small cell Lung diseases Lung Neoplasms - genetics Lung Neoplasms - pathology Medical diagnosis Medical prognosis Metastases Metastasis Mice MicroRNAs Mutation Mutation, Missense Neoplasm Metastasis - genetics Non-small cell lung carcinoma Oncology Oncology/Lung Cancer Transcription Tumor proteins Tumor Suppressor Protein p53 - genetics Tumors Validation studies |
| title | Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma |
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