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 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
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series Molecular Carcinogenesis
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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.
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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