author_facet Szeliga, Monika
Zgrzywa, Agata
Obara‐Michlewska, Marta
Albrecht, Jan
Szeliga, Monika
Zgrzywa, Agata
Obara‐Michlewska, Marta
Albrecht, Jan
author Szeliga, Monika
Zgrzywa, Agata
Obara‐Michlewska, Marta
Albrecht, Jan
spellingShingle Szeliga, Monika
Zgrzywa, Agata
Obara‐Michlewska, Marta
Albrecht, Jan
Journal of Neurochemistry
Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
Cellular and Molecular Neuroscience
Biochemistry
author_sort szeliga, monika
spelling Szeliga, Monika Zgrzywa, Agata Obara‐Michlewska, Marta Albrecht, Jan 0022-3042 1471-4159 Wiley Cellular and Molecular Neuroscience Biochemistry http://dx.doi.org/10.1111/j.1471-4159.2012.07917.x <jats:title>Abstract</jats:title><jats:p>O<jats:sup>6</jats:sup>‐methylguanine‐<jats:styled-content style="fixed-case">DNA</jats:styled-content> methyltransferase (<jats:styled-content style="fixed-case">MGMT</jats:styled-content>) is a <jats:styled-content style="fixed-case">DNA</jats:styled-content>‐repair protein promoting resistance of tumor cells to alkylating chemotherapeutic agents. Glioma cells are particularly resistant to this class of drugs which include temozolomide (<jats:styled-content style="fixed-case">TMZ</jats:styled-content>) and carmustine (<jats:styled-content style="fixed-case">BCNU</jats:styled-content>). A previous study using the RNA microarray technique showed that decrease of <jats:styled-content style="fixed-case">MGMT mRNA</jats:styled-content> stands out among the alterations in gene expression caused by the cell growth‐depressing transfection of a T98G glioma cell line with liver‐type glutaminase (<jats:styled-content style="fixed-case">LGA</jats:styled-content>) [Szeliga <jats:italic>et al</jats:italic>. (2009) <jats:italic>Glia</jats:italic>, 57, 1014]. Here, we show that stably <jats:styled-content style="fixed-case">LGA</jats:styled-content>‐transfected cells (<jats:styled-content style="fixed-case">TLGA</jats:styled-content>) exhibit decreased <jats:styled-content style="fixed-case">MGMT</jats:styled-content> protein expression and activity as compared with non‐transfected or mock transfected cells (controls). However, the decrease of expression occurs in the absence of changes in the methylation of the promoter region, indicating that <jats:styled-content style="fixed-case">LGA</jats:styled-content> circumvents, by an as yet unknown route, the most common mechanism of MGMT silencing. TLGA turned out to be significantly more sensitive to treatment with 100–1000 μM of <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content> in the acute cell growth inhibition assay (<jats:styled-content style="fixed-case">MTT</jats:styled-content>). In the clonogenic survival assay, <jats:styled-content style="fixed-case">TLGA</jats:styled-content> cells displayed increased sensitivity even to 10 μM <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content>. Our results indicate that enrichment with <jats:styled-content style="fixed-case">LGA</jats:styled-content>, in addition to inhibiting glioma growth, may facilitate chemotherapeutic intervention.</jats:p> Transfection of a human glioblastoma cell line with liver‐type glutaminase (<scp>LGA</scp>) down‐regulates the expression of <scp>DNA</scp>‐repair gene <scp>MGMT</scp> and sensitizes the cells to alkylating agents Journal of Neurochemistry
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series Journal of Neurochemistry
source_id 49
title Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_unstemmed Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_full Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_fullStr Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_full_unstemmed Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_short Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_sort transfection of a human glioblastoma cell line with liver‐type glutaminase (<scp>lga</scp>) down‐regulates the expression of <scp>dna</scp>‐repair gene <scp>mgmt</scp> and sensitizes the cells to alkylating agents
topic Cellular and Molecular Neuroscience
Biochemistry
url http://dx.doi.org/10.1111/j.1471-4159.2012.07917.x
publishDate 2012
physical 428-436
description <jats:title>Abstract</jats:title><jats:p>O<jats:sup>6</jats:sup>‐methylguanine‐<jats:styled-content style="fixed-case">DNA</jats:styled-content> methyltransferase (<jats:styled-content style="fixed-case">MGMT</jats:styled-content>) is a <jats:styled-content style="fixed-case">DNA</jats:styled-content>‐repair protein promoting resistance of tumor cells to alkylating chemotherapeutic agents. Glioma cells are particularly resistant to this class of drugs which include temozolomide (<jats:styled-content style="fixed-case">TMZ</jats:styled-content>) and carmustine (<jats:styled-content style="fixed-case">BCNU</jats:styled-content>). A previous study using the RNA microarray technique showed that decrease of <jats:styled-content style="fixed-case">MGMT mRNA</jats:styled-content> stands out among the alterations in gene expression caused by the cell growth‐depressing transfection of a T98G glioma cell line with liver‐type glutaminase (<jats:styled-content style="fixed-case">LGA</jats:styled-content>) [Szeliga <jats:italic>et al</jats:italic>. (2009) <jats:italic>Glia</jats:italic>, 57, 1014]. Here, we show that stably <jats:styled-content style="fixed-case">LGA</jats:styled-content>‐transfected cells (<jats:styled-content style="fixed-case">TLGA</jats:styled-content>) exhibit decreased <jats:styled-content style="fixed-case">MGMT</jats:styled-content> protein expression and activity as compared with non‐transfected or mock transfected cells (controls). However, the decrease of expression occurs in the absence of changes in the methylation of the promoter region, indicating that <jats:styled-content style="fixed-case">LGA</jats:styled-content> circumvents, by an as yet unknown route, the most common mechanism of MGMT silencing. TLGA turned out to be significantly more sensitive to treatment with 100–1000 μM of <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content> in the acute cell growth inhibition assay (<jats:styled-content style="fixed-case">MTT</jats:styled-content>). In the clonogenic survival assay, <jats:styled-content style="fixed-case">TLGA</jats:styled-content> cells displayed increased sensitivity even to 10 μM <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content>. Our results indicate that enrichment with <jats:styled-content style="fixed-case">LGA</jats:styled-content>, in addition to inhibiting glioma growth, may facilitate chemotherapeutic intervention.</jats:p>
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author Szeliga, Monika, Zgrzywa, Agata, Obara‐Michlewska, Marta, Albrecht, Jan
author_facet Szeliga, Monika, Zgrzywa, Agata, Obara‐Michlewska, Marta, Albrecht, Jan, Szeliga, Monika, Zgrzywa, Agata, Obara‐Michlewska, Marta, Albrecht, Jan
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description <jats:title>Abstract</jats:title><jats:p>O<jats:sup>6</jats:sup>‐methylguanine‐<jats:styled-content style="fixed-case">DNA</jats:styled-content> methyltransferase (<jats:styled-content style="fixed-case">MGMT</jats:styled-content>) is a <jats:styled-content style="fixed-case">DNA</jats:styled-content>‐repair protein promoting resistance of tumor cells to alkylating chemotherapeutic agents. Glioma cells are particularly resistant to this class of drugs which include temozolomide (<jats:styled-content style="fixed-case">TMZ</jats:styled-content>) and carmustine (<jats:styled-content style="fixed-case">BCNU</jats:styled-content>). A previous study using the RNA microarray technique showed that decrease of <jats:styled-content style="fixed-case">MGMT mRNA</jats:styled-content> stands out among the alterations in gene expression caused by the cell growth‐depressing transfection of a T98G glioma cell line with liver‐type glutaminase (<jats:styled-content style="fixed-case">LGA</jats:styled-content>) [Szeliga <jats:italic>et al</jats:italic>. (2009) <jats:italic>Glia</jats:italic>, 57, 1014]. Here, we show that stably <jats:styled-content style="fixed-case">LGA</jats:styled-content>‐transfected cells (<jats:styled-content style="fixed-case">TLGA</jats:styled-content>) exhibit decreased <jats:styled-content style="fixed-case">MGMT</jats:styled-content> protein expression and activity as compared with non‐transfected or mock transfected cells (controls). However, the decrease of expression occurs in the absence of changes in the methylation of the promoter region, indicating that <jats:styled-content style="fixed-case">LGA</jats:styled-content> circumvents, by an as yet unknown route, the most common mechanism of MGMT silencing. TLGA turned out to be significantly more sensitive to treatment with 100–1000 μM of <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content> in the acute cell growth inhibition assay (<jats:styled-content style="fixed-case">MTT</jats:styled-content>). In the clonogenic survival assay, <jats:styled-content style="fixed-case">TLGA</jats:styled-content> cells displayed increased sensitivity even to 10 μM <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content>. Our results indicate that enrichment with <jats:styled-content style="fixed-case">LGA</jats:styled-content>, in addition to inhibiting glioma growth, may facilitate chemotherapeutic intervention.</jats:p>
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spelling Szeliga, Monika Zgrzywa, Agata Obara‐Michlewska, Marta Albrecht, Jan 0022-3042 1471-4159 Wiley Cellular and Molecular Neuroscience Biochemistry http://dx.doi.org/10.1111/j.1471-4159.2012.07917.x <jats:title>Abstract</jats:title><jats:p>O<jats:sup>6</jats:sup>‐methylguanine‐<jats:styled-content style="fixed-case">DNA</jats:styled-content> methyltransferase (<jats:styled-content style="fixed-case">MGMT</jats:styled-content>) is a <jats:styled-content style="fixed-case">DNA</jats:styled-content>‐repair protein promoting resistance of tumor cells to alkylating chemotherapeutic agents. Glioma cells are particularly resistant to this class of drugs which include temozolomide (<jats:styled-content style="fixed-case">TMZ</jats:styled-content>) and carmustine (<jats:styled-content style="fixed-case">BCNU</jats:styled-content>). A previous study using the RNA microarray technique showed that decrease of <jats:styled-content style="fixed-case">MGMT mRNA</jats:styled-content> stands out among the alterations in gene expression caused by the cell growth‐depressing transfection of a T98G glioma cell line with liver‐type glutaminase (<jats:styled-content style="fixed-case">LGA</jats:styled-content>) [Szeliga <jats:italic>et al</jats:italic>. (2009) <jats:italic>Glia</jats:italic>, 57, 1014]. Here, we show that stably <jats:styled-content style="fixed-case">LGA</jats:styled-content>‐transfected cells (<jats:styled-content style="fixed-case">TLGA</jats:styled-content>) exhibit decreased <jats:styled-content style="fixed-case">MGMT</jats:styled-content> protein expression and activity as compared with non‐transfected or mock transfected cells (controls). However, the decrease of expression occurs in the absence of changes in the methylation of the promoter region, indicating that <jats:styled-content style="fixed-case">LGA</jats:styled-content> circumvents, by an as yet unknown route, the most common mechanism of MGMT silencing. TLGA turned out to be significantly more sensitive to treatment with 100–1000 μM of <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content> in the acute cell growth inhibition assay (<jats:styled-content style="fixed-case">MTT</jats:styled-content>). In the clonogenic survival assay, <jats:styled-content style="fixed-case">TLGA</jats:styled-content> cells displayed increased sensitivity even to 10 μM <jats:styled-content style="fixed-case">TMZ</jats:styled-content> and <jats:styled-content style="fixed-case">BCNU</jats:styled-content>. Our results indicate that enrichment with <jats:styled-content style="fixed-case">LGA</jats:styled-content>, in addition to inhibiting glioma growth, may facilitate chemotherapeutic intervention.</jats:p> Transfection of a human glioblastoma cell line with liver‐type glutaminase (<scp>LGA</scp>) down‐regulates the expression of <scp>DNA</scp>‐repair gene <scp>MGMT</scp> and sensitizes the cells to alkylating agents Journal of Neurochemistry
spellingShingle Szeliga, Monika, Zgrzywa, Agata, Obara‐Michlewska, Marta, Albrecht, Jan, Journal of Neurochemistry, Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents, Cellular and Molecular Neuroscience, Biochemistry
title Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_full Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_fullStr Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_full_unstemmed Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_short Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
title_sort transfection of a human glioblastoma cell line with liver‐type glutaminase (<scp>lga</scp>) down‐regulates the expression of <scp>dna</scp>‐repair gene <scp>mgmt</scp> and sensitizes the cells to alkylating agents
title_unstemmed Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents
topic Cellular and Molecular Neuroscience, Biochemistry
url http://dx.doi.org/10.1111/j.1471-4159.2012.07917.x