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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...
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Zeitschriftentitel: | Journal of Neurochemistry |
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Personen und Körperschaften: | , , , |
In: | Journal of Neurochemistry, 123, 2012, 3, S. 428-436 |
Format: | E-Article |
Sprache: | Englisch |
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Wiley
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author_facet |
Szeliga, Monika Zgrzywa, Agata Obara‐Michlewska, Marta Albrecht, Jan Szeliga, Monika Zgrzywa, Agata Obara‐Michlewska, Marta Albrecht, Jan |
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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 |
doi_str_mv |
10.1111/j.1471-4159.2012.07917.x |
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Psychologie Chemie und Pharmazie Biologie |
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imprint |
Wiley, 2012 |
imprint_str_mv |
Wiley, 2012 |
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0022-3042 1471-4159 |
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0022-3042 1471-4159 |
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szeliga2012transfectionofahumanglioblastomacelllinewithlivertypeglutaminaselgadownregulatestheexpressionofdnarepairgenemgmtandsensitizesthecellstoalkylatingagents |
publishDateSort |
2012 |
publisher |
Wiley |
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ai |
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ai |
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 |
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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 |