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

被引：111

作者：

Gao, Qing ^{[1
]}

Steine, Eveline J. ^{[1
]}

Barrasa, M. Inmaculada ^{[1
]}

Hockemeyer, Dirk ^{[1
]}

Pawlak, Mathias ^{[1
]}

Fu, Dongdong ^{[1
]}

Reddy, Seshamma ^{[1
]}

Bell, George W. ^{[1
]}

Jaenisch, Rudolf ^{[1
,2
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 44期

基金：

美国国家卫生研究院;

关键词：

adenocarcinoma; cancer epigenetics; gene body methylation; K-ras; STEM-CELLS; METHYLATION; EXPRESSION; MOUSE; MUTATIONS; 3B; 3A; EPIGENETICS; LESIONS; MODELS;

D O I：

10.1073/pnas.1114946108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：18061 / 18066

页数：6

共 36 条

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