MGMT hypermethylation and MDR system in glioblastoma cancer stem cells
Cancer stem cells (CSCs) in gliomas are associated with resistance to radio- and chemotherapy, based on O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation and the Multidrug resistance (MDR) system activation. Samples from 21 glioblastomas (GBMs) were put in culture with growth factors...
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Veröffentlicht in: | Cancer genomics & proteomics 2012-07, Vol.9 (4), p.171-178 |
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creator | Caldera, Valentina Mellai, Marta Annovazzi, Laura Monzeglio, Oriana Piazzi, Angela Schiffer, Davide |
description | Cancer stem cells (CSCs) in gliomas are associated with resistance to radio- and chemotherapy, based on O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation and the Multidrug resistance (MDR) system activation.
Samples from 21 glioblastomas (GBMs) were put in culture with growth factors or serum in order to obtain neurospheres or adherent cells. Both were genetically and immunohistochemically characterized for ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), ATP-binding cassette, sub-family C (CFTR/MRP), member 1 (ABCC1) and MGMT expression together with primary tumors.
ABCB1 expression was positive in endothelial cells of primary tumors. ABCC1 expression was variably positive in tumor cells and positive in neurospheres, and less expressed in adherent cells. MGMT was methylated and unmethylated in primary tumors and in neurospheres, respectively, and unmethylated in adherent cells.
Methylation is an epigenetic event affecting progenitors before the separation of the two glia lineages and maximally the future initiating cells. ABCB1 expression is limited to endothelial cells, whereas ABCC1 expression could mark a minority of tumor cells approaching a stem-like status. |
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Samples from 21 glioblastomas (GBMs) were put in culture with growth factors or serum in order to obtain neurospheres or adherent cells. Both were genetically and immunohistochemically characterized for ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), ATP-binding cassette, sub-family C (CFTR/MRP), member 1 (ABCC1) and MGMT expression together with primary tumors.
ABCB1 expression was positive in endothelial cells of primary tumors. ABCC1 expression was variably positive in tumor cells and positive in neurospheres, and less expressed in adherent cells. MGMT was methylated and unmethylated in primary tumors and in neurospheres, respectively, and unmethylated in adherent cells.
Methylation is an epigenetic event affecting progenitors before the separation of the two glia lineages and maximally the future initiating cells. ABCB1 expression is limited to endothelial cells, whereas ABCC1 expression could mark a minority of tumor cells approaching a stem-like status.</description><identifier>ISSN: 1109-6535</identifier><identifier>EISSN: 1790-6245</identifier><identifier>PMID: 22798502</identifier><language>eng</language><publisher>Greece</publisher><subject>Adult ; Aged ; Aged, 80 and over ; ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; Brain Neoplasms - metabolism ; Cells, Cultured ; DNA Methylation ; DNA Modification Methylases - genetics ; DNA Modification Methylases - metabolism ; DNA Repair Enzymes - genetics ; DNA Repair Enzymes - metabolism ; Drug Resistance, Multiple - genetics ; Female ; Gene Expression Regulation, Neoplastic ; Glioblastoma - metabolism ; Humans ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins - genetics ; Multidrug Resistance-Associated Proteins - metabolism ; Neoplastic Stem Cells - metabolism ; Promoter Regions, Genetic ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Cancer genomics & proteomics, 2012-07, Vol.9 (4), p.171-178</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22798502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caldera, Valentina</creatorcontrib><creatorcontrib>Mellai, Marta</creatorcontrib><creatorcontrib>Annovazzi, Laura</creatorcontrib><creatorcontrib>Monzeglio, Oriana</creatorcontrib><creatorcontrib>Piazzi, Angela</creatorcontrib><creatorcontrib>Schiffer, Davide</creatorcontrib><title>MGMT hypermethylation and MDR system in glioblastoma cancer stem cells</title><title>Cancer genomics & proteomics</title><addtitle>Cancer Genomics Proteomics</addtitle><description>Cancer stem cells (CSCs) in gliomas are associated with resistance to radio- and chemotherapy, based on O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation and the Multidrug resistance (MDR) system activation.
Samples from 21 glioblastomas (GBMs) were put in culture with growth factors or serum in order to obtain neurospheres or adherent cells. Both were genetically and immunohistochemically characterized for ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), ATP-binding cassette, sub-family C (CFTR/MRP), member 1 (ABCC1) and MGMT expression together with primary tumors.
ABCB1 expression was positive in endothelial cells of primary tumors. ABCC1 expression was variably positive in tumor cells and positive in neurospheres, and less expressed in adherent cells. MGMT was methylated and unmethylated in primary tumors and in neurospheres, respectively, and unmethylated in adherent cells.
Methylation is an epigenetic event affecting progenitors before the separation of the two glia lineages and maximally the future initiating cells. ABCB1 expression is limited to endothelial cells, whereas ABCC1 expression could mark a minority of tumor cells approaching a stem-like status.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>ATP Binding Cassette Transporter, Sub-Family B</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Brain Neoplasms - metabolism</subject><subject>Cells, Cultured</subject><subject>DNA Methylation</subject><subject>DNA Modification Methylases - genetics</subject><subject>DNA Modification Methylases - metabolism</subject><subject>DNA Repair Enzymes - genetics</subject><subject>DNA Repair Enzymes - metabolism</subject><subject>Drug Resistance, Multiple - genetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glioblastoma - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>1109-6535</issn><issn>1790-6245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j01Lw0AYhBdRbK3-Bdmjl8B-b_Yo1bZCgyD1HN7NvrGRfJlNDvn3Vq2nGZiHYeaCLLl1LDFC6cuT58wlRku9IDcxfjKmrFTsmiyEsC7VTCzJJttmB3qcexwaHI9zDWPVtRTaQLOnNxrnOGJDq5Z-1FXna4hj1wAtoC1woL9ZgXUdb8lVCXXEu7OuyPvm-bDeJfvX7cv6cZ_0gvMxKSy3HgpuTVAejNTGaOPRINrCSAhQKomMeZUa7bRTwoTSM0QZmEZWglyRh7_efui-Joxj3lTxZwG02E0x50yK1KlU2hN6f0Yn32DI-6FqYJjz_-_yG42HVkE</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Caldera, Valentina</creator><creator>Mellai, Marta</creator><creator>Annovazzi, Laura</creator><creator>Monzeglio, Oriana</creator><creator>Piazzi, Angela</creator><creator>Schiffer, Davide</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20120701</creationdate><title>MGMT hypermethylation and MDR system in glioblastoma cancer stem cells</title><author>Caldera, Valentina ; Mellai, Marta ; Annovazzi, Laura ; Monzeglio, Oriana ; Piazzi, Angela ; Schiffer, Davide</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-c717bac176d4ba6356656be6ee7c63adaf43e00b4865959426dfb0ee3d05e0fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>ATP Binding Cassette Transporter, Sub-Family B</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Brain Neoplasms - metabolism</topic><topic>Cells, Cultured</topic><topic>DNA Methylation</topic><topic>DNA Modification Methylases - genetics</topic><topic>DNA Modification Methylases - metabolism</topic><topic>DNA Repair Enzymes - genetics</topic><topic>DNA Repair Enzymes - metabolism</topic><topic>Drug Resistance, Multiple - genetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glioblastoma - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caldera, Valentina</creatorcontrib><creatorcontrib>Mellai, Marta</creatorcontrib><creatorcontrib>Annovazzi, Laura</creatorcontrib><creatorcontrib>Monzeglio, Oriana</creatorcontrib><creatorcontrib>Piazzi, Angela</creatorcontrib><creatorcontrib>Schiffer, Davide</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Cancer genomics & proteomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caldera, Valentina</au><au>Mellai, Marta</au><au>Annovazzi, Laura</au><au>Monzeglio, Oriana</au><au>Piazzi, Angela</au><au>Schiffer, Davide</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MGMT hypermethylation and MDR system in glioblastoma cancer stem cells</atitle><jtitle>Cancer genomics & proteomics</jtitle><addtitle>Cancer Genomics Proteomics</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>9</volume><issue>4</issue><spage>171</spage><epage>178</epage><pages>171-178</pages><issn>1109-6535</issn><eissn>1790-6245</eissn><abstract>Cancer stem cells (CSCs) in gliomas are associated with resistance to radio- and chemotherapy, based on O(6)-methylguanine-DNA methyltransferase (MGMT) hypermethylation and the Multidrug resistance (MDR) system activation.
Samples from 21 glioblastomas (GBMs) were put in culture with growth factors or serum in order to obtain neurospheres or adherent cells. Both were genetically and immunohistochemically characterized for ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), ATP-binding cassette, sub-family C (CFTR/MRP), member 1 (ABCC1) and MGMT expression together with primary tumors.
ABCB1 expression was positive in endothelial cells of primary tumors. ABCC1 expression was variably positive in tumor cells and positive in neurospheres, and less expressed in adherent cells. MGMT was methylated and unmethylated in primary tumors and in neurospheres, respectively, and unmethylated in adherent cells.
Methylation is an epigenetic event affecting progenitors before the separation of the two glia lineages and maximally the future initiating cells. ABCB1 expression is limited to endothelial cells, whereas ABCC1 expression could mark a minority of tumor cells approaching a stem-like status.</abstract><cop>Greece</cop><pmid>22798502</pmid><tpages>8</tpages></addata></record> |
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subjects | Adult Aged Aged, 80 and over ATP Binding Cassette Transporter, Sub-Family B ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Brain Neoplasms - metabolism Cells, Cultured DNA Methylation DNA Modification Methylases - genetics DNA Modification Methylases - metabolism DNA Repair Enzymes - genetics DNA Repair Enzymes - metabolism Drug Resistance, Multiple - genetics Female Gene Expression Regulation, Neoplastic Glioblastoma - metabolism Humans Male Middle Aged Multidrug Resistance-Associated Proteins - genetics Multidrug Resistance-Associated Proteins - metabolism Neoplastic Stem Cells - metabolism Promoter Regions, Genetic Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism |
title | MGMT hypermethylation and MDR system in glioblastoma cancer stem cells |
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