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Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence
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Zeitschriftentitel: | Molecular Carcinogenesis |
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Personen und Körperschaften: | , , , , , |
In: | Molecular Carcinogenesis, 46, 2007, 9, S. 766-772 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Wiley
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Schlagwörter: |
author_facet |
Schmidt, Wolfgang M. Sedivy, Roland Forstner, Birgit Steger, Günther G. Zöchbauer‐Müller, Sabine Mader, Robert M. Schmidt, Wolfgang M. Sedivy, Roland Forstner, Birgit Steger, Günther G. Zöchbauer‐Müller, Sabine Mader, Robert M. |
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author |
Schmidt, Wolfgang M. Sedivy, Roland Forstner, Birgit Steger, Günther G. Zöchbauer‐Müller, Sabine Mader, Robert M. |
spellingShingle |
Schmidt, Wolfgang M. Sedivy, Roland Forstner, Birgit Steger, Günther G. Zöchbauer‐Müller, Sabine Mader, Robert M. Molecular Carcinogenesis Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence Cancer Research Molecular Biology |
author_sort |
schmidt, wolfgang m. |
spelling |
Schmidt, Wolfgang M. Sedivy, Roland Forstner, Birgit Steger, Günther G. Zöchbauer‐Müller, Sabine Mader, Robert M. 0899-1987 1098-2744 Wiley Cancer Research Molecular Biology http://dx.doi.org/10.1002/mc.20307 <jats:title>Abstract</jats:title><jats:p>Epigenetic silencing is a prominent feature of cancer. Here, we investigated the expression of DNA demethylase and three DNA methyltransferases during colorectal tumorigenesis comparing the genes encoding DNA methyltransferases 1 (<jats:italic>DNMT1</jats:italic>), 3A, and 3B (<jats:italic>DNMT3A</jats:italic> and <jats:italic>DNMT3B</jats:italic>) with methyl‐CpG binding domain protein 2 (<jats:italic>MBD2</jats:italic>), recently described as the only active DNA demethylase. Total RNA isolated from normal colonic mucosa (<jats:italic>n</jats:italic> = 24), benign adenomas (<jats:italic>n</jats:italic> = 18), and malignant colorectal carcinomas (<jats:italic>n</jats:italic> = 32) was analyzed by reverse transcriptase‐PCR with subsequent quantification by capillary gel electrophoresis. In contrast to <jats:italic>MBD2</jats:italic>, expression of <jats:italic>DNMT1</jats:italic> and <jats:italic>DNMT3A</jats:italic> increased in parallel to the degree of dysplasia, with significant overexpression in the malignant lesion when compared with mucosa or with benign lesions (<jats:italic>DNMT1</jats:italic>). Pairwise comparisons between tumors and matched, adjacent healthy mucosa tissue (<jats:italic>n</jats:italic> = 13) revealed that expression of all three genes encoding DNA methyltransferases increased by two‐ to three‐fold. Our data suggest a relevant role of the DNA methyltransferases during colorectal tumorigenesis. This increase is not counterbalanced by enhanced expression of the demethylating component MBD2. As a consequence, epigenetic regulation in the adenoma‐carcinoma sequence may be driven by increased methylating activity rather than suppressed demethylation. © 2007 Wiley‐Liss, Inc.</jats:p> Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence Molecular Carcinogenesis |
doi_str_mv |
10.1002/mc.20307 |
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Online |
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Medizin Biologie |
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Wiley, 2007 |
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2007 |
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Wiley |
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Molecular Carcinogenesis |
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49 |
title |
Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_unstemmed |
Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_full |
Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_fullStr |
Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_full_unstemmed |
Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_short |
Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_sort |
progressive up‐regulation of genes encoding dna methyltransferases in the colorectal adenoma‐carcinoma sequence |
topic |
Cancer Research Molecular Biology |
url |
http://dx.doi.org/10.1002/mc.20307 |
publishDate |
2007 |
physical |
766-772 |
description |
<jats:title>Abstract</jats:title><jats:p>Epigenetic silencing is a prominent feature of cancer. Here, we investigated the expression of DNA demethylase and three DNA methyltransferases during colorectal tumorigenesis comparing the genes encoding DNA methyltransferases 1 (<jats:italic>DNMT1</jats:italic>), 3A, and 3B (<jats:italic>DNMT3A</jats:italic> and <jats:italic>DNMT3B</jats:italic>) with methyl‐CpG binding domain protein 2 (<jats:italic>MBD2</jats:italic>), recently described as the only active DNA demethylase. Total RNA isolated from normal colonic mucosa (<jats:italic>n</jats:italic> = 24), benign adenomas (<jats:italic>n</jats:italic> = 18), and malignant colorectal carcinomas (<jats:italic>n</jats:italic> = 32) was analyzed by reverse transcriptase‐PCR with subsequent quantification by capillary gel electrophoresis. In contrast to <jats:italic>MBD2</jats:italic>, expression of <jats:italic>DNMT1</jats:italic> and <jats:italic>DNMT3A</jats:italic> increased in parallel to the degree of dysplasia, with significant overexpression in the malignant lesion when compared with mucosa or with benign lesions (<jats:italic>DNMT1</jats:italic>). Pairwise comparisons between tumors and matched, adjacent healthy mucosa tissue (<jats:italic>n</jats:italic> = 13) revealed that expression of all three genes encoding DNA methyltransferases increased by two‐ to three‐fold. Our data suggest a relevant role of the DNA methyltransferases during colorectal tumorigenesis. This increase is not counterbalanced by enhanced expression of the demethylating component MBD2. As a consequence, epigenetic regulation in the adenoma‐carcinoma sequence may be driven by increased methylating activity rather than suppressed demethylation. © 2007 Wiley‐Liss, Inc.</jats:p> |
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author | Schmidt, Wolfgang M., Sedivy, Roland, Forstner, Birgit, Steger, Günther G., Zöchbauer‐Müller, Sabine, Mader, Robert M. |
author_facet | Schmidt, Wolfgang M., Sedivy, Roland, Forstner, Birgit, Steger, Günther G., Zöchbauer‐Müller, Sabine, Mader, Robert M., Schmidt, Wolfgang M., Sedivy, Roland, Forstner, Birgit, Steger, Günther G., Zöchbauer‐Müller, Sabine, Mader, Robert M. |
author_sort | schmidt, wolfgang m. |
container_issue | 9 |
container_start_page | 766 |
container_title | Molecular Carcinogenesis |
container_volume | 46 |
description | <jats:title>Abstract</jats:title><jats:p>Epigenetic silencing is a prominent feature of cancer. Here, we investigated the expression of DNA demethylase and three DNA methyltransferases during colorectal tumorigenesis comparing the genes encoding DNA methyltransferases 1 (<jats:italic>DNMT1</jats:italic>), 3A, and 3B (<jats:italic>DNMT3A</jats:italic> and <jats:italic>DNMT3B</jats:italic>) with methyl‐CpG binding domain protein 2 (<jats:italic>MBD2</jats:italic>), recently described as the only active DNA demethylase. Total RNA isolated from normal colonic mucosa (<jats:italic>n</jats:italic> = 24), benign adenomas (<jats:italic>n</jats:italic> = 18), and malignant colorectal carcinomas (<jats:italic>n</jats:italic> = 32) was analyzed by reverse transcriptase‐PCR with subsequent quantification by capillary gel electrophoresis. In contrast to <jats:italic>MBD2</jats:italic>, expression of <jats:italic>DNMT1</jats:italic> and <jats:italic>DNMT3A</jats:italic> increased in parallel to the degree of dysplasia, with significant overexpression in the malignant lesion when compared with mucosa or with benign lesions (<jats:italic>DNMT1</jats:italic>). Pairwise comparisons between tumors and matched, adjacent healthy mucosa tissue (<jats:italic>n</jats:italic> = 13) revealed that expression of all three genes encoding DNA methyltransferases increased by two‐ to three‐fold. Our data suggest a relevant role of the DNA methyltransferases during colorectal tumorigenesis. This increase is not counterbalanced by enhanced expression of the demethylating component MBD2. As a consequence, epigenetic regulation in the adenoma‐carcinoma sequence may be driven by increased methylating activity rather than suppressed demethylation. © 2007 Wiley‐Liss, Inc.</jats:p> |
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spelling | Schmidt, Wolfgang M. Sedivy, Roland Forstner, Birgit Steger, Günther G. Zöchbauer‐Müller, Sabine Mader, Robert M. 0899-1987 1098-2744 Wiley Cancer Research Molecular Biology http://dx.doi.org/10.1002/mc.20307 <jats:title>Abstract</jats:title><jats:p>Epigenetic silencing is a prominent feature of cancer. Here, we investigated the expression of DNA demethylase and three DNA methyltransferases during colorectal tumorigenesis comparing the genes encoding DNA methyltransferases 1 (<jats:italic>DNMT1</jats:italic>), 3A, and 3B (<jats:italic>DNMT3A</jats:italic> and <jats:italic>DNMT3B</jats:italic>) with methyl‐CpG binding domain protein 2 (<jats:italic>MBD2</jats:italic>), recently described as the only active DNA demethylase. Total RNA isolated from normal colonic mucosa (<jats:italic>n</jats:italic> = 24), benign adenomas (<jats:italic>n</jats:italic> = 18), and malignant colorectal carcinomas (<jats:italic>n</jats:italic> = 32) was analyzed by reverse transcriptase‐PCR with subsequent quantification by capillary gel electrophoresis. In contrast to <jats:italic>MBD2</jats:italic>, expression of <jats:italic>DNMT1</jats:italic> and <jats:italic>DNMT3A</jats:italic> increased in parallel to the degree of dysplasia, with significant overexpression in the malignant lesion when compared with mucosa or with benign lesions (<jats:italic>DNMT1</jats:italic>). Pairwise comparisons between tumors and matched, adjacent healthy mucosa tissue (<jats:italic>n</jats:italic> = 13) revealed that expression of all three genes encoding DNA methyltransferases increased by two‐ to three‐fold. Our data suggest a relevant role of the DNA methyltransferases during colorectal tumorigenesis. This increase is not counterbalanced by enhanced expression of the demethylating component MBD2. As a consequence, epigenetic regulation in the adenoma‐carcinoma sequence may be driven by increased methylating activity rather than suppressed demethylation. © 2007 Wiley‐Liss, Inc.</jats:p> Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence Molecular Carcinogenesis |
spellingShingle | Schmidt, Wolfgang M., Sedivy, Roland, Forstner, Birgit, Steger, Günther G., Zöchbauer‐Müller, Sabine, Mader, Robert M., Molecular Carcinogenesis, Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence, Cancer Research, Molecular Biology |
title | Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_full | Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_fullStr | Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_full_unstemmed | Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_short | Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_sort | progressive up‐regulation of genes encoding dna methyltransferases in the colorectal adenoma‐carcinoma sequence |
title_unstemmed | Progressive up‐regulation of genes encoding DNA methyltransferases in the colorectal adenoma‐carcinoma sequence |
topic | Cancer Research, Molecular Biology |
url | http://dx.doi.org/10.1002/mc.20307 |