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Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide
BACKGROUND: The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) can cause resistance to the alkylating drug temozolomide (TMZ). The purpose of this study was to determine the relationship between the MGMT status, determined by means of several techniques and methods, and the cytot...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905289/ https://www.ncbi.nlm.nih.gov/pubmed/20517307 http://dx.doi.org/10.1038/sj.bjc.6605712 |
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author | van Nifterik, K A van den Berg, J van der Meide, W F Ameziane, N Wedekind, L E Steenbergen, R D M Leenstra, S Lafleur, M V M Slotman, B J Stalpers, L J A Sminia, P |
author_facet | van Nifterik, K A van den Berg, J van der Meide, W F Ameziane, N Wedekind, L E Steenbergen, R D M Leenstra, S Lafleur, M V M Slotman, B J Stalpers, L J A Sminia, P |
author_sort | van Nifterik, K A |
collection | PubMed |
description | BACKGROUND: The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) can cause resistance to the alkylating drug temozolomide (TMZ). The purpose of this study was to determine the relationship between the MGMT status, determined by means of several techniques and methods, and the cytotoxic response to TMZ in 11 glioblastoma multiforme (GBM) cell lines and 5 human tumour cell lines of other origins. METHODS: Cell survival was analysed by clonogenic assay. The MGMT protein levels were assessed by western blot analysis. The MGMT promoter methylation levels were determined using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and quantitative real-time methylation-specific PCR (qMSP). On the basis of the results of these techniques, six GBM cell lines were selected and subjected to bisulphite sequencing. RESULTS: The MGMT protein was detected in all TMZ-resistant cell lines, whereas no MGMT protein could be detected in cell lines that were TMZ sensitive. The MS-MLPA results were able to predict TMZ sensitivity in 9 out of 16 cell lines (56%). The qMSP results matched well with TMZ sensitivity in 11 out of 12 (92%) glioma cell lines. In addition, methylation as detected by bisulphite sequencing seemed to be predictive of TMZ sensitivity in all six cell lines analysed (100%). CONCLUSION: The MGMT protein expression more than MGMT promoter methylation status predicts the response to TMZ in human tumour cell lines. |
format | Text |
id | pubmed-2905289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-29052892011-06-29 Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide van Nifterik, K A van den Berg, J van der Meide, W F Ameziane, N Wedekind, L E Steenbergen, R D M Leenstra, S Lafleur, M V M Slotman, B J Stalpers, L J A Sminia, P Br J Cancer Translational Therapeutics BACKGROUND: The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) can cause resistance to the alkylating drug temozolomide (TMZ). The purpose of this study was to determine the relationship between the MGMT status, determined by means of several techniques and methods, and the cytotoxic response to TMZ in 11 glioblastoma multiforme (GBM) cell lines and 5 human tumour cell lines of other origins. METHODS: Cell survival was analysed by clonogenic assay. The MGMT protein levels were assessed by western blot analysis. The MGMT promoter methylation levels were determined using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and quantitative real-time methylation-specific PCR (qMSP). On the basis of the results of these techniques, six GBM cell lines were selected and subjected to bisulphite sequencing. RESULTS: The MGMT protein was detected in all TMZ-resistant cell lines, whereas no MGMT protein could be detected in cell lines that were TMZ sensitive. The MS-MLPA results were able to predict TMZ sensitivity in 9 out of 16 cell lines (56%). The qMSP results matched well with TMZ sensitivity in 11 out of 12 (92%) glioma cell lines. In addition, methylation as detected by bisulphite sequencing seemed to be predictive of TMZ sensitivity in all six cell lines analysed (100%). CONCLUSION: The MGMT protein expression more than MGMT promoter methylation status predicts the response to TMZ in human tumour cell lines. Nature Publishing Group 2010-06-29 2010-06-01 /pmc/articles/PMC2905289/ /pubmed/20517307 http://dx.doi.org/10.1038/sj.bjc.6605712 Text en Copyright © 2010 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Translational Therapeutics van Nifterik, K A van den Berg, J van der Meide, W F Ameziane, N Wedekind, L E Steenbergen, R D M Leenstra, S Lafleur, M V M Slotman, B J Stalpers, L J A Sminia, P Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide |
title | Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide |
title_full | Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide |
title_fullStr | Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide |
title_full_unstemmed | Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide |
title_short | Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide |
title_sort | absence of the mgmt protein as well as methylation of the mgmt promoter predict the sensitivity for temozolomide |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905289/ https://www.ncbi.nlm.nih.gov/pubmed/20517307 http://dx.doi.org/10.1038/sj.bjc.6605712 |
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