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Publication : Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression.

First Author  Gao Q Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  44 Pages  18061-6
PubMed ID  22011581 Mgi Jnum  J:180053
Mgi Id  MGI:5305351 Doi  10.1073/pnas.1114946108
Citation  Gao Q, et al. (2011) Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression. Proc Natl Acad Sci U S A 108(44):18061-6
abstractText  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.
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