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
Hauptverfasser: Caldera, Valentina, Mellai, Marta, Annovazzi, Laura, Monzeglio, Oriana, Piazzi, Angela, Schiffer, Davide
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container_end_page 178
container_issue 4
container_start_page 171
container_title Cancer genomics & proteomics
container_volume 9
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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source MEDLINE; EZB-FREE-00999 freely available EZB journals
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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