Evidence that SOX2 overexpression is oncogenic in the lung
SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung. We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is u...
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| Veröffentlicht in: | PloS one 2010-06, Vol.5 (6), p.e11022-e11022 |
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| creator | Lu, Yun Futtner, Christopher Rock, Jason R Xu, Xia Whitworth, Walter Hogan, Brigid L M Onaitis, Mark W |
| description | SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung.
We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63).
These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer. |
| doi_str_mv | 10.1371/journal.pone.0011022 |
| format | Article |
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We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63).
These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0011022</identifier><identifier>PMID: 20548776</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Alveoli ; Analysis ; Animal models ; Animals ; Breast cancer ; Cell Biology ; Cell Biology/Gene Expression ; Consortia ; Datasets ; Decision making ; Development and progression ; Epithelial cells ; Epithelium ; Gene expression ; Genetics and Genomics/Cancer Genetics ; Genetics and Genomics/Disease Models ; Genetics and Genomics/Gene Expression ; Genetics and Genomics/Genomics ; Genetics and Genomics/Medical Genetics ; Genomics ; Hyperplasia ; Immunohistochemistry ; Keratin ; Lung - metabolism ; Lung cancer ; Lung Neoplasms - genetics ; Lungs ; Medical prognosis ; Metastasis ; Mice ; Mice, Transgenic ; Models, Animal ; Oncogenes ; Oncology/Lung Cancer ; Polymerase Chain Reaction ; Respiratory Medicine/Lung Cancer ; Rodents ; Solid tumors ; SOXB1 Transcription Factors - genetics ; Stains & staining ; Stem cell transplantation ; Stem cells ; Surgery ; Trachea ; Transgenic animals ; Tumors</subject><ispartof>PloS one, 2010-06, Vol.5 (6), p.e11022-e11022</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (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>Lu et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-e4a3b82a30c18d4b4c9753b97e921e71d13c0fb2cc0f85a5c0beaf9151a8b48d3</citedby><cites>FETCH-LOGICAL-c723t-e4a3b82a30c18d4b4c9753b97e921e71d13c0fb2cc0f85a5c0beaf9151a8b48d3</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/PMC2883553/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883553/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20548776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Navarro, Alfons</contributor><creatorcontrib>Lu, Yun</creatorcontrib><creatorcontrib>Futtner, Christopher</creatorcontrib><creatorcontrib>Rock, Jason R</creatorcontrib><creatorcontrib>Xu, Xia</creatorcontrib><creatorcontrib>Whitworth, Walter</creatorcontrib><creatorcontrib>Hogan, Brigid L M</creatorcontrib><creatorcontrib>Onaitis, Mark W</creatorcontrib><title>Evidence that SOX2 overexpression is oncogenic in the lung</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung.
We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63).
These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer.</description><subject>Adenocarcinoma</subject><subject>Alveoli</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Breast cancer</subject><subject>Cell Biology</subject><subject>Cell Biology/Gene Expression</subject><subject>Consortia</subject><subject>Datasets</subject><subject>Decision making</subject><subject>Development and progression</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Gene expression</subject><subject>Genetics and Genomics/Cancer Genetics</subject><subject>Genetics and Genomics/Disease Models</subject><subject>Genetics and Genomics/Gene Expression</subject><subject>Genetics and Genomics/Genomics</subject><subject>Genetics and Genomics/Medical Genetics</subject><subject>Genomics</subject><subject>Hyperplasia</subject><subject>Immunohistochemistry</subject><subject>Keratin</subject><subject>Lung - metabolism</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lungs</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Models, Animal</subject><subject>Oncogenes</subject><subject>Oncology/Lung Cancer</subject><subject>Polymerase Chain Reaction</subject><subject>Respiratory Medicine/Lung Cancer</subject><subject>Rodents</subject><subject>Solid tumors</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>Stains & staining</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Surgery</subject><subject>Trachea</subject><subject>Transgenic animals</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLguLFjPlomsQLYVlWHVgYcFW8C2l62snQScakHdZ_b8bpLlNZUAJJOHneN1_nZNlzjOaYcvxu7YfgdDffegdzhDBGhDzITrGkZFYSRB8ezU-yJzGuEWJUlOXj7IQgVgjOy9Ps_eXO1uAM5P1K9_n18gfJ_Q4C3GwDxGi9y23MvTO-BWdNbl0CIe8G1z7NHjW6i_BsHM-ybx8vv158nl0tPy0uzq9mhhPaz6DQtBJEU2SwqIuqMJIzWkkOkmDguMbUoKYiJvWCaWZQBbqRmGEtqkLU9Cx7efDddj6q8dpRYZL0klHME7E4ELXXa7UNdqPDL-W1VX8CPrRKh96aDlRhACNEcM0rUYChUjS0wZQJUWpda5q8Poy7DdUGagOuD7qbmE5XnF2p1u8UEYIytjd4MxoE_3OA2KuNjQa6TjvwQ1S8KHFJpJT_JimliHDCEvnqL_L-ZxipVqebWtf4dECz91TnBadCJiecqPk9VGo1bKxJydTYFJ8I3k4Eienhpm_1EKNaXH_5f3b5fcq-PmJXoLt-FX039Cnp4hQsDqAJPsYAzd1vYKT2tXD7GmpfC2qshSR7cfyTd6Lb5Ke_ARgnAhU</recordid><startdate>20100610</startdate><enddate>20100610</enddate><creator>Lu, Yun</creator><creator>Futtner, Christopher</creator><creator>Rock, Jason R</creator><creator>Xu, Xia</creator><creator>Whitworth, Walter</creator><creator>Hogan, Brigid L M</creator><creator>Onaitis, Mark W</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>AEUYN</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>7TO</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100610</creationdate><title>Evidence that SOX2 overexpression is oncogenic in the lung</title><author>Lu, Yun ; Futtner, Christopher ; Rock, Jason R ; Xu, Xia ; Whitworth, Walter ; Hogan, Brigid L M ; Onaitis, Mark W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c723t-e4a3b82a30c18d4b4c9753b97e921e71d13c0fb2cc0f85a5c0beaf9151a8b48d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adenocarcinoma</topic><topic>Alveoli</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Breast cancer</topic><topic>Cell Biology</topic><topic>Cell Biology/Gene Expression</topic><topic>Consortia</topic><topic>Datasets</topic><topic>Decision making</topic><topic>Development and progression</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Gene expression</topic><topic>Genetics and Genomics/Cancer Genetics</topic><topic>Genetics and Genomics/Disease Models</topic><topic>Genetics and Genomics/Gene Expression</topic><topic>Genetics and Genomics/Genomics</topic><topic>Genetics and Genomics/Medical Genetics</topic><topic>Genomics</topic><topic>Hyperplasia</topic><topic>Immunohistochemistry</topic><topic>Keratin</topic><topic>Lung - 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Academic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Yun</au><au>Futtner, Christopher</au><au>Rock, Jason R</au><au>Xu, Xia</au><au>Whitworth, Walter</au><au>Hogan, Brigid L M</au><au>Onaitis, Mark W</au><au>Navarro, Alfons</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence that SOX2 overexpression is oncogenic in the lung</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-06-10</date><risdate>2010</risdate><volume>5</volume><issue>6</issue><spage>e11022</spage><epage>e11022</epage><pages>e11022-e11022</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung.
We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63).
These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20548776</pmid><doi>10.1371/journal.pone.0011022</doi><tpages>e11022</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Alveoli Analysis Animal models Animals Breast cancer Cell Biology Cell Biology/Gene Expression Consortia Datasets Decision making Development and progression Epithelial cells Epithelium Gene expression Genetics and Genomics/Cancer Genetics Genetics and Genomics/Disease Models Genetics and Genomics/Gene Expression Genetics and Genomics/Genomics Genetics and Genomics/Medical Genetics Genomics Hyperplasia Immunohistochemistry Keratin Lung - metabolism Lung cancer Lung Neoplasms - genetics Lungs Medical prognosis Metastasis Mice Mice, Transgenic Models, Animal Oncogenes Oncology/Lung Cancer Polymerase Chain Reaction Respiratory Medicine/Lung Cancer Rodents Solid tumors SOXB1 Transcription Factors - genetics Stains & staining Stem cell transplantation Stem cells Surgery Trachea Transgenic animals Tumors |
| title | Evidence that SOX2 overexpression is oncogenic in the lung |
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