PT  - JOURNAL ARTICLE
AU  - VALENTINA CALDERA
AU  - MARTA MELLAI
AU  - LAURA ANNOVAZZI
AU  - ORIANA MONZEGLIO
AU  - ANGELA PIAZZI
AU  - DAVIDE SCHIFFER
TI  - <em>MGMT</em> Hypermethylation and MDR System in Glioblastoma Cancer Stem Cells
DP  - 2012 Jul 01
TA  - Cancer Genomics - Proteomics
PG  - 171--178
VI  - 9
IP  - 4
4099  - http://cgp.iiarjournals.org/content/9/4/171.short
4100  - http://cgp.iiarjournals.org/content/9/4/171.full
SO  - Cancer Genomics Proteomics2012 Jul 01; 9
AB  - Background: Cancer stem cells (CSCs) in gliomas are associated with resistance to radio- and chemotherapy, based on O6-methylguanine-DNA methyltransferase (MGMT) hypermethylation and the Multidrug resistance (MDR) system activation. Materials and Methods: 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. Results: 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. Conclusion: 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.