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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Generation of Cancerous Neural Stem Cells Forming Glial Tumor by Oncogenic Stimulation</title>
<author><name sortKey="Lee, Ji Seon" sort="Lee, Ji Seon" uniqKey="Lee J" first="Ji-Seon" last="Lee">Ji-Seon Lee</name>
</author>
<author><name sortKey="Lee, Hong Jun" sort="Lee, Hong Jun" uniqKey="Lee H" first="Hong Jun" last="Lee">Hong Jun Lee</name>
</author>
<author><name sortKey="Moon, Bo Hyun" sort="Moon, Bo Hyun" uniqKey="Moon B" first="Bo-Hyun" last="Moon">Bo-Hyun Moon</name>
</author>
<author><name sortKey="Song, Seung Hyun" sort="Song, Seung Hyun" uniqKey="Song S" first="Seung-Hyun" last="Song">Seung-Hyun Song</name>
</author>
<author><name sortKey="Lee, Mi Ok" sort="Lee, Mi Ok" uniqKey="Lee M" first="Mi-Ok" last="Lee">Mi-Ok Lee</name>
</author>
<author><name sortKey="Shim, Sung Han" sort="Shim, Sung Han" uniqKey="Shim S" first="Sung Han" last="Shim">Sung Han Shim</name>
</author>
<author><name sortKey="Kim, Hyung Seok" sort="Kim, Hyung Seok" uniqKey="Kim H" first="Hyung Seok" last="Kim">Hyung Seok Kim</name>
</author>
<author><name sortKey="Lee, Min Cheol" sort="Lee, Min Cheol" uniqKey="Lee M" first="Min Cheol" last="Lee">Min Cheol Lee</name>
</author>
<author><name sortKey="Kwon, Jeong Taik" sort="Kwon, Jeong Taik" uniqKey="Kwon J" first="Jeong Taik" last="Kwon">Jeong Taik Kwon</name>
</author>
<author><name sortKey="Fornace, Albert J" sort="Fornace, Albert J" uniqKey="Fornace A" first="Albert J." last="Fornace">Albert J. Fornace</name>
</author>
<author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name>
</author>
<author><name sortKey="Cha, Hyuk Jin" sort="Cha, Hyuk Jin" uniqKey="Cha H" first="Hyuk Jin" last="Cha">Hyuk Jin Cha</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21755312</idno>
<idno type="pmc">4043123</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043123</idno>
<idno type="RBID">PMC:4043123</idno>
<idno type="doi">10.1007/s12015-011-9280-4</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000753</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000753</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Generation of Cancerous Neural Stem Cells Forming Glial Tumor by Oncogenic Stimulation</title>
<author><name sortKey="Lee, Ji Seon" sort="Lee, Ji Seon" uniqKey="Lee J" first="Ji-Seon" last="Lee">Ji-Seon Lee</name>
</author>
<author><name sortKey="Lee, Hong Jun" sort="Lee, Hong Jun" uniqKey="Lee H" first="Hong Jun" last="Lee">Hong Jun Lee</name>
</author>
<author><name sortKey="Moon, Bo Hyun" sort="Moon, Bo Hyun" uniqKey="Moon B" first="Bo-Hyun" last="Moon">Bo-Hyun Moon</name>
</author>
<author><name sortKey="Song, Seung Hyun" sort="Song, Seung Hyun" uniqKey="Song S" first="Seung-Hyun" last="Song">Seung-Hyun Song</name>
</author>
<author><name sortKey="Lee, Mi Ok" sort="Lee, Mi Ok" uniqKey="Lee M" first="Mi-Ok" last="Lee">Mi-Ok Lee</name>
</author>
<author><name sortKey="Shim, Sung Han" sort="Shim, Sung Han" uniqKey="Shim S" first="Sung Han" last="Shim">Sung Han Shim</name>
</author>
<author><name sortKey="Kim, Hyung Seok" sort="Kim, Hyung Seok" uniqKey="Kim H" first="Hyung Seok" last="Kim">Hyung Seok Kim</name>
</author>
<author><name sortKey="Lee, Min Cheol" sort="Lee, Min Cheol" uniqKey="Lee M" first="Min Cheol" last="Lee">Min Cheol Lee</name>
</author>
<author><name sortKey="Kwon, Jeong Taik" sort="Kwon, Jeong Taik" uniqKey="Kwon J" first="Jeong Taik" last="Kwon">Jeong Taik Kwon</name>
</author>
<author><name sortKey="Fornace, Albert J" sort="Fornace, Albert J" uniqKey="Fornace A" first="Albert J." last="Fornace">Albert J. Fornace</name>
</author>
<author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name>
</author>
<author><name sortKey="Cha, Hyuk Jin" sort="Cha, Hyuk Jin" uniqKey="Cha H" first="Hyuk Jin" last="Cha">Hyuk Jin Cha</name>
</author>
</analytic>
<series><title level="j">Stem cell reviews</title>
<idno type="ISSN">1550-8943</idno>
<idno type="eISSN">1558-6804</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
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<front><div type="abstract" xml:lang="en"><p id="P1">Neural stem cells in the brain have been shown to be ‘cells of origin’ of certain brain cancers, most notably astrocytomas and medulloblastoma. In particular, in a mouse model, the targeting of genetic modifications for astrocytoma-relevant tumor suppressors to neural stem cells causes malignant astrocytoma to arise, thereby suggesting that astrocytoma is derived from neural stem cells. However, it remains to be determined whether this important finding is reproducible in humans. Herein, we generated cancerous neural stem cells by introducing a set of oncogenes to human fetal neural stem cells (hfNSCs). Serial genetic modification with v-myc for immortalization and consequent H-Ras for oncogenic stimulation with viral gene delivery proved sufficient to induce the transformation of hfNSCs. The resultant F3.Ras cells evidenced a variety of the hallmarks of brain cancer stem cells and most importantly were tumorigenic, forming brain cancers consisting of both a large number of differentiated and a very few undifferentiated populations of cells in an in vivo mouse model. On the contrary, oligodendrocytes derived from the v-myc expressing parent neural stem cells were not transformed by H-Ras, which suggests that neural stem cells may be more susceptible to cancerous transformation by a combination of oncogenes. We also determined that v-myc expressing fetal neural stem cells were defective in p53 response upon the introduction of H-Ras; this finding suggests that an insufficient p53-dependent tumor suppressive mechanism would be associated with high oncogenic susceptibility to H-Ras introduction.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101255952</journal-id>
<journal-id journal-id-type="pubmed-jr-id">33156</journal-id>
<journal-id journal-id-type="nlm-ta">Stem Cell Rev</journal-id>
<journal-id journal-id-type="iso-abbrev">Stem Cell Rev</journal-id>
<journal-title-group><journal-title>Stem cell reviews</journal-title>
</journal-title-group>
<issn pub-type="ppub">1550-8943</issn>
<issn pub-type="epub">1558-6804</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21755312</article-id>
<article-id pub-id-type="pmc">4043123</article-id>
<article-id pub-id-type="doi">10.1007/s12015-011-9280-4</article-id>
<article-id pub-id-type="manuscript">NIHMS464162</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Generation of Cancerous Neural Stem Cells Forming Glial Tumor by Oncogenic Stimulation</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Ji-Seon</given-names>
</name>
<aff id="A1">Department of Life Sciences, Sogang University, Seoul 121–742, Korea</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Hong Jun</given-names>
</name>
<aff id="A2">Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea. Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC V6T 2B5, Canada</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Moon</surname>
<given-names>Bo-Hyun</given-names>
</name>
<aff id="A3">Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, USA</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Song</surname>
<given-names>Seung-Hyun</given-names>
</name>
<aff id="A4">Department of Biomedical Sciences, CHA University, Seoul, Korea</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Mi-Ok</given-names>
</name>
<aff id="A5">Department of Biomedical Sciences, CHA University, Seoul, Korea</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Shim</surname>
<given-names>Sung Han</given-names>
</name>
<aff id="A6">Department of Biomedical Sciences, CHA University, Seoul, Korea</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Hyung Seok</given-names>
</name>
<aff id="A7">Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea</aff>
<email>sukim@interchange.ubc.ca</email>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Min Cheol</given-names>
</name>
<aff id="A8">Department of Pathology, Chonnam National University Medical School, Gwangju, Korea</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Kwon</surname>
<given-names>Jeong Taik</given-names>
</name>
<aff id="A9">Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Fornace</surname>
<given-names>Albert J.</given-names>
<suffix>Jr.</suffix>
</name>
<aff id="A10">Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, USA</aff>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Seung U.</given-names>
</name>
<aff id="A11">Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea. Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC V6T 2B5, Canada</aff>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Cha</surname>
<given-names>Hyuk Jin</given-names>
</name>
<aff id="A12">Department of Life Sciences, Sogang University, Seoul 121–742, Korea</aff>
<email>hjcha@sogang.ac.kr</email>
</contrib>
</contrib-group>
<author-notes><fn id="FN1" fn-type="equal"><p>Ji-Seon Lee and Hong Jun Lee contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>15</day>
<month>5</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub"><month>6</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>03</day>
<month>6</month>
<year>2014</year>
</pub-date>
<volume>8</volume>
<issue>2</issue>
<fpage>532</fpage>
<lpage>545</lpage>
<pmc-comment>elocation-id from pubmed: 10.1007/s12015-011-9280-4</pmc-comment>
<permissions><copyright-statement>© Springer Science+Business Media, LLC 2011</copyright-statement>
<copyright-year>2011</copyright-year>
</permissions>
<abstract><p id="P1">Neural stem cells in the brain have been shown to be ‘cells of origin’ of certain brain cancers, most notably astrocytomas and medulloblastoma. In particular, in a mouse model, the targeting of genetic modifications for astrocytoma-relevant tumor suppressors to neural stem cells causes malignant astrocytoma to arise, thereby suggesting that astrocytoma is derived from neural stem cells. However, it remains to be determined whether this important finding is reproducible in humans. Herein, we generated cancerous neural stem cells by introducing a set of oncogenes to human fetal neural stem cells (hfNSCs). Serial genetic modification with v-myc for immortalization and consequent H-Ras for oncogenic stimulation with viral gene delivery proved sufficient to induce the transformation of hfNSCs. The resultant F3.Ras cells evidenced a variety of the hallmarks of brain cancer stem cells and most importantly were tumorigenic, forming brain cancers consisting of both a large number of differentiated and a very few undifferentiated populations of cells in an in vivo mouse model. On the contrary, oligodendrocytes derived from the v-myc expressing parent neural stem cells were not transformed by H-Ras, which suggests that neural stem cells may be more susceptible to cancerous transformation by a combination of oncogenes. We also determined that v-myc expressing fetal neural stem cells were defective in p53 response upon the introduction of H-Ras; this finding suggests that an insufficient p53-dependent tumor suppressive mechanism would be associated with high oncogenic susceptibility to H-Ras introduction.</p>
</abstract>
<kwd-group><kwd>Human neural stem cells</kwd>
<kwd>v-myc</kwd>
<kwd>H-Ras</kwd>
<kwd>Cancerous stem cells</kwd>
<kwd>p53</kwd>
<kwd>Glial tumor</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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