HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation
Malignant glioma is the most common brain tumor with 16 000 new cases diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9783 tissue samples from the GeneSapiens database to systematically identify genes that are most glioma-specific....
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| Veröffentlicht in: | Oncogene 2012-03, Vol.31 (10), p.1299-1310 |
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| creator | Haapa-Paananen, S Kiviluoto, S Waltari, M Puputti, M Mpindi, J P Kohonen, P Tynninen, O Haapasalo, H Joensuu, H Perälä, M Kallioniemi, O |
| description | Malignant glioma is the most common brain tumor with 16 000 new cases diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9783 tissue samples from the GeneSapiens database to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared with 425 samples from histologically normal central nervous system. Transcription cofactor
HES6
(hairy and enhancer of split 6) emerged as the most glioma-specific gene. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was expressed in endothelial cells of the normal brain and glioma tissue. Recurrent grade 2 astrocytomas and grade 2 or 3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. High
HES6
mRNA expression correlated with the proneural subtype that generally has a favorable outcome but is prone to recur. Functional studies suggested an important role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and migration after HES6 silencing. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc and nuclear factor-κB transcriptional networks. We conclude that HES6 is important for glioma cell proliferation and migration, and may have a role in angiogenesis. |
| doi_str_mv | 10.1038/onc.2011.316 |
| format | Article |
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HES6
(hairy and enhancer of split 6) emerged as the most glioma-specific gene. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was expressed in endothelial cells of the normal brain and glioma tissue. Recurrent grade 2 astrocytomas and grade 2 or 3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. High
HES6
mRNA expression correlated with the proneural subtype that generally has a favorable outcome but is prone to recur. Functional studies suggested an important role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and migration after HES6 silencing. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc and nuclear factor-κB transcriptional networks. We conclude that HES6 is important for glioma cell proliferation and migration, and may have a role in angiogenesis.</description><identifier>ISSN: 0950-9232</identifier><identifier>ISSN: 1476-5594</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2011.316</identifier><identifier>PMID: 21785461</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Angiogenesis ; Apoptosis ; Astrocytoma ; Basic Helix-Loop-Helix Transcription Factors - analysis ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - physiology ; Brain cancer ; Brain Neoplasms - genetics ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Brain tumors ; c-Myc protein ; Cell Biology ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Cell Proliferation ; Cells ; Central nervous system ; DNA microarrays ; Endothelial cells ; Enhancer-of-split protein ; ErbB Receptors - genetics ; Gene Dosage ; Gene expression ; Genes ; Genes, myc ; Genetic aspects ; Genetic transcription ; Genomes ; Glioblastoma ; Glioma ; Glioma - genetics ; Glioma - mortality ; Glioma - pathology ; Glioma cells ; Gliomas ; Hes6 gene ; Human Genetics ; Humans ; Immunoreactivity ; Internal Medicine ; Medicine ; Medicine & Public Health ; Myc protein ; Oncology ; original-article ; p53 Protein ; Physiological aspects ; Receptor, Platelet-Derived Growth Factor alpha - genetics ; Repressor Proteins - analysis ; Repressor Proteins - genetics ; Repressor Proteins - physiology ; Ribonucleic acid ; Risk factors ; RNA ; Transcription, Genetic ; Transcriptomics ; Tumors ; Vascular Endothelial Growth Factor Receptor-2 - genetics</subject><ispartof>Oncogene, 2012-03, Vol.31 (10), p.1299-1310</ispartof><rights>Macmillan Publishers Limited 2012</rights><rights>COPYRIGHT 2012 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2012.</rights><rights>Copyright Nature Publishing Group Mar 8, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-dea92a5559eea6189582f3b8e6dfdd3f9af259449ac14fadd1a9320e1be1767c3</citedby><cites>FETCH-LOGICAL-c520t-dea92a5559eea6189582f3b8e6dfdd3f9af259449ac14fadd1a9320e1be1767c3</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.2011.316$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2011.316$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21785461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haapa-Paananen, S</creatorcontrib><creatorcontrib>Kiviluoto, S</creatorcontrib><creatorcontrib>Waltari, M</creatorcontrib><creatorcontrib>Puputti, M</creatorcontrib><creatorcontrib>Mpindi, J P</creatorcontrib><creatorcontrib>Kohonen, P</creatorcontrib><creatorcontrib>Tynninen, O</creatorcontrib><creatorcontrib>Haapasalo, H</creatorcontrib><creatorcontrib>Joensuu, H</creatorcontrib><creatorcontrib>Perälä, M</creatorcontrib><creatorcontrib>Kallioniemi, O</creatorcontrib><title>HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Malignant glioma is the most common brain tumor with 16 000 new cases diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9783 tissue samples from the GeneSapiens database to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared with 425 samples from histologically normal central nervous system. Transcription cofactor
HES6
(hairy and enhancer of split 6) emerged as the most glioma-specific gene. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was expressed in endothelial cells of the normal brain and glioma tissue. Recurrent grade 2 astrocytomas and grade 2 or 3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. High
HES6
mRNA expression correlated with the proneural subtype that generally has a favorable outcome but is prone to recur. Functional studies suggested an important role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and migration after HES6 silencing. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc and nuclear factor-κB transcriptional networks. We conclude that HES6 is important for glioma cell proliferation and migration, and may have a role in angiogenesis.</description><subject>Angiogenesis</subject><subject>Apoptosis</subject><subject>Astrocytoma</subject><subject>Basic Helix-Loop-Helix Transcription Factors - analysis</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - physiology</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain tumors</subject><subject>c-Myc protein</subject><subject>Cell Biology</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cells</subject><subject>Central nervous system</subject><subject>DNA microarrays</subject><subject>Endothelial cells</subject><subject>Enhancer-of-split protein</subject><subject>ErbB Receptors - genetics</subject><subject>Gene Dosage</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genes, myc</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Genomes</subject><subject>Glioblastoma</subject><subject>Glioma</subject><subject>Glioma - genetics</subject><subject>Glioma - mortality</subject><subject>Glioma - pathology</subject><subject>Glioma cells</subject><subject>Gliomas</subject><subject>Hes6 gene</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunoreactivity</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Myc protein</subject><subject>Oncology</subject><subject>original-article</subject><subject>p53 Protein</subject><subject>Physiological aspects</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - genetics</subject><subject>Repressor Proteins - analysis</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - physiology</subject><subject>Ribonucleic acid</subject><subject>Risk factors</subject><subject>RNA</subject><subject>Transcription, Genetic</subject><subject>Transcriptomics</subject><subject>Tumors</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - genetics</subject><issn>0950-9232</issn><issn>1476-5594</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFks1vFSEUxYnR2Gd159oQXbjpPIFhmGHZNNWaNHGhrgkPLhMaBkaY19iNf7tMXj-iqTEsCJffuZdDDkKvKdlS0g4fUjRbRijdtlQ8QRvKe9F0neRP0YbIjjSStewIvSjlihDSS8KeoyNG-6Hjgm7Qr4vzrwKPEAH7ggsEMIu_hnCD0zVk-DlnKAUs9hGPwadJYx0tzrDWIS6lHrGf5pQXHRe8ZB2LyX5efIo6VG7cB72kjJO70885Be8g65V5iZ45HQq8ut2P0feP59_OLprLL58-n51eNqZjZGksaMl0V20BaEEH2Q3MtbsBhHXWtk5qx6plLrWh3GlrqZYtI0B3QHvRm_YYvT_0rdN_7KEsavLFQAg6QtoXJcVAheCy_z_JejEIzmkl3_5FXqV9rrZXSEjaSSEq9O5fEBOccs4Gxh6oUQdQPrpUf9Ksg9UpG9qedH0rK7V9hKrLwuRNiuB8rf8hODkITE6lZHBqzn7S-UZRotbwqBoetYZH1fBU_M3tW_e7Cew9fJeWCjQHoNSrOEJ-MPNow9-i986z</recordid><startdate>20120308</startdate><enddate>20120308</enddate><creator>Haapa-Paananen, S</creator><creator>Kiviluoto, S</creator><creator>Waltari, M</creator><creator>Puputti, M</creator><creator>Mpindi, J P</creator><creator>Kohonen, P</creator><creator>Tynninen, O</creator><creator>Haapasalo, H</creator><creator>Joensuu, H</creator><creator>Perälä, M</creator><creator>Kallioniemi, O</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>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></search><sort><creationdate>20120308</creationdate><title>HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation</title><author>Haapa-Paananen, S ; Kiviluoto, S ; Waltari, M ; Puputti, M ; Mpindi, J P ; Kohonen, P ; Tynninen, O ; Haapasalo, H ; Joensuu, H ; Perälä, M ; Kallioniemi, O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-dea92a5559eea6189582f3b8e6dfdd3f9af259449ac14fadd1a9320e1be1767c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Angiogenesis</topic><topic>Apoptosis</topic><topic>Astrocytoma</topic><topic>Basic Helix-Loop-Helix Transcription Factors - analysis</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - physiology</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain tumors</topic><topic>c-Myc protein</topic><topic>Cell Biology</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cells</topic><topic>Central nervous system</topic><topic>DNA microarrays</topic><topic>Endothelial cells</topic><topic>Enhancer-of-split protein</topic><topic>ErbB Receptors - genetics</topic><topic>Gene Dosage</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genes, myc</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Genomes</topic><topic>Glioblastoma</topic><topic>Glioma</topic><topic>Glioma - genetics</topic><topic>Glioma - 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Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haapa-Paananen, S</au><au>Kiviluoto, S</au><au>Waltari, M</au><au>Puputti, M</au><au>Mpindi, J P</au><au>Kohonen, P</au><au>Tynninen, O</au><au>Haapasalo, H</au><au>Joensuu, H</au><au>Perälä, M</au><au>Kallioniemi, O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2012-03-08</date><risdate>2012</risdate><volume>31</volume><issue>10</issue><spage>1299</spage><epage>1310</epage><pages>1299-1310</pages><issn>0950-9232</issn><issn>1476-5594</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Malignant glioma is the most common brain tumor with 16 000 new cases diagnosed annually in the United States. We performed a systematic large-scale transcriptomics data mining study of 9783 tissue samples from the GeneSapiens database to systematically identify genes that are most glioma-specific. We searched for genes that were highly expressed in 322 glioblastoma multiforme tissue samples and 66 anaplastic astrocytomas as compared with 425 samples from histologically normal central nervous system. Transcription cofactor
HES6
(hairy and enhancer of split 6) emerged as the most glioma-specific gene. Immunostaining of a tissue microarray showed HES6 expression in 335 (98.8%) out of the 339 glioma samples. HES6 was expressed in endothelial cells of the normal brain and glioma tissue. Recurrent grade 2 astrocytomas and grade 2 or 3 oligodendrogliomas showed higher levels of HES6 immunoreactivity than the corresponding primary tumors. High
HES6
mRNA expression correlated with the proneural subtype that generally has a favorable outcome but is prone to recur. Functional studies suggested an important role for HES6 in supporting survival of glioma cells, as evidenced by reduction of cancer cell proliferation and migration after HES6 silencing. The biological role and consequences of HES6 silencing and overexpression was explored with genome-wide analyses, which implicated a role for HES6 in p53, c-myc and nuclear factor-κB transcriptional networks. We conclude that HES6 is important for glioma cell proliferation and migration, and may have a role in angiogenesis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21785461</pmid><doi>10.1038/onc.2011.316</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-9232 |
| ispartof | Oncogene, 2012-03, Vol.31 (10), p.1299-1310 |
| issn | 0950-9232 1476-5594 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_968166497 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; EZB-FREE-00999 freely available EZB journals |
| subjects | Angiogenesis Apoptosis Astrocytoma Basic Helix-Loop-Helix Transcription Factors - analysis Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - physiology Brain cancer Brain Neoplasms - genetics Brain Neoplasms - mortality Brain Neoplasms - pathology Brain tumors c-Myc protein Cell Biology Cell growth Cell Line, Tumor Cell migration Cell Movement Cell Proliferation Cells Central nervous system DNA microarrays Endothelial cells Enhancer-of-split protein ErbB Receptors - genetics Gene Dosage Gene expression Genes Genes, myc Genetic aspects Genetic transcription Genomes Glioblastoma Glioma Glioma - genetics Glioma - mortality Glioma - pathology Glioma cells Gliomas Hes6 gene Human Genetics Humans Immunoreactivity Internal Medicine Medicine Medicine & Public Health Myc protein Oncology original-article p53 Protein Physiological aspects Receptor, Platelet-Derived Growth Factor alpha - genetics Repressor Proteins - analysis Repressor Proteins - genetics Repressor Proteins - physiology Ribonucleic acid Risk factors RNA Transcription, Genetic Transcriptomics Tumors Vascular Endothelial Growth Factor Receptor-2 - genetics |
| title | HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation |
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