Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression
Alterations in DNA methylation have been associated with genome-wide hypomethylation and regional de novo methylation in numerous cancers. De novo methylation is mediated by the de novo methyltransferases Dnmt3a and 3b, but only Dnmt3b has been implicated in promoting cancer by silencing of tumor-su...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2012
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| Online Access: | http://hdl.handle.net/1721.1/73173 |
| _version_ | 1826205466065108992 |
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| author | Gao, Qing Steine, Eveline J. Barrasa, M. Inmaculada Hockemeyer, Dirk Pawlak, Mathias Fu, Dongdong Reddy, Seshamma Bell, George W. Jaenisch, Rudolf |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gao, Qing Steine, Eveline J. Barrasa, M. Inmaculada Hockemeyer, Dirk Pawlak, Mathias Fu, Dongdong Reddy, Seshamma Bell, George W. Jaenisch, Rudolf |
| author_sort | Gao, Qing |
| collection | MIT |
| description | Alterations in DNA methylation have been associated with genome-wide hypomethylation and regional de novo methylation in numerous cancers. De novo methylation is mediated by the de novo methyltransferases Dnmt3a and 3b, but only Dnmt3b has been implicated in promoting cancer by silencing of tumor-suppressor genes. In this study, we have analyzed the role of Dnmt3a in lung cancer by using a conditional mouse tumor model. We show that Dnmt3a deficiency significantly promotes tumor growth and progression but not initiation. Changes in gene expression show that Dnmt3a deficiency affects key steps in cancer progression, such as angiogenesis, cell adhesion, and cell motion, consistent with accelerated and more malignant growth. Our results suggest that Dnmt3a may act like a tumor-suppressor gene in lung tumor progression and may be a critical determinant of lung cancer malignancy. |
| first_indexed | 2024-09-23T13:13:17Z |
| format | Article |
| id | mit-1721.1/73173 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:13:17Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/731732022-10-01T13:49:48Z Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression Gao, Qing Steine, Eveline J. Barrasa, M. Inmaculada Hockemeyer, Dirk Pawlak, Mathias Fu, Dongdong Reddy, Seshamma Bell, George W. Jaenisch, Rudolf Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Jaenisch, Rudolf Alterations in DNA methylation have been associated with genome-wide hypomethylation and regional de novo methylation in numerous cancers. De novo methylation is mediated by the de novo methyltransferases Dnmt3a and 3b, but only Dnmt3b has been implicated in promoting cancer by silencing of tumor-suppressor genes. In this study, we have analyzed the role of Dnmt3a in lung cancer by using a conditional mouse tumor model. We show that Dnmt3a deficiency significantly promotes tumor growth and progression but not initiation. Changes in gene expression show that Dnmt3a deficiency affects key steps in cancer progression, such as angiogenesis, cell adhesion, and cell motion, consistent with accelerated and more malignant growth. Our results suggest that Dnmt3a may act like a tumor-suppressor gene in lung tumor progression and may be a critical determinant of lung cancer malignancy. National Institutes of Health (U.S.) (Grant R01-CA087869) 2012-09-26T13:38:16Z 2012-09-26T13:38:16Z 2011-10 2011-06 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/73173 Gao, Q. et al. “Deletion of the De Novo DNA Methyltransferase Dnmt3a Promotes Lung Tumor Progression.” Proceedings of the National Academy of Sciences 108.44 (2011): 18061–18066. Copyright ©2011 by the National Academy of Sciences 22011581 en_US http://dx.doi.org/10.1073/pnas.1114946108 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Gao, Qing Steine, Eveline J. Barrasa, M. Inmaculada Hockemeyer, Dirk Pawlak, Mathias Fu, Dongdong Reddy, Seshamma Bell, George W. Jaenisch, Rudolf Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression |
| title | Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression |
| title_full | Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression |
| title_fullStr | Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression |
| title_full_unstemmed | Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression |
| title_short | Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression |
| title_sort | deletion of the de novo dna methyltransferase dnmt3a promotes lung tumor progression |
| url | http://hdl.handle.net/1721.1/73173 |
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