Interplay between Menin and K-Ras in Regulating Lung Adenocarcinoma

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	Interplay between Menin and K-Ras in Regulating Lung Adenocarcinoma
	Wu, Yuan ; Feng, Zi-Jie ; Gao, Shu-Bin ; Matkar, Smita ; Xu, Bin ; Duan, Hong-Bin ; Lin, Xiao ; Li, Shan-Hua ; Hua, Xianxin ; Jin, Guang-Hui ; Jin GH(金光辉)
刊名	http://dx.doi.org/10.1074/jbc.M112.382416
	2012-11-16
关键词	NUCLEOTIDE EXCHANGE FACTOR HISTONE METHYLATION HUMAN CANCER GENE PROTEIN GROWTH EXPRESSION GRB2 CELLS SOS
英文摘要	Natural Science Foundation of China [81071926, 81272719, 81101763, 81101924]; Natural Science Foundation of Fujian Province [2011J06016]; Natural Science Foundation of Xiamen [3502Z20104001]; Fundamental Research Grant for the central universities, Xiamen University [2010121106]; National Institutes of Health [R01 DK085121]; Lung Cancer Research Foundation Grant; MEN1, which encodes the nuclear protein menin, acts as a tumor suppressor in lung cancer and is often inactivated in human primary lung adenocarcinoma. Here, we show that the inactivation of MEN1 is associated with increased DNA methylation at the MEN1 promoter by K-Ras. On one hand, the activated K-Ras up-regulates the expression of DNA methyltransferases and enhances the binding of DNA methyltransferase 1 to the MEN1 promoter, leading to increased DNA methylation at the MEN1 gene in lung cancer cells; on the other hand, menin reduces the level of active Ras-GTP at least partly by preventing GRB2 and SOS1 from binding to Ras, without affecting the expression of GRB2 and SOS1. In human lung adenocarcinoma samples, we further demonstrate that reduced menin expression is associated with the enhanced expression of Ras (p < 0.05). Finally, excision of the Men1 gene markedly accelerates the K-Ras(G12D)-induced tumor formation in the Men1(f/f); K-Ras(G12D/+); Cre ER mouse model. Together, these findings uncover a previously unknown link between activated K-Ras and menin, an important interplay governing tumor activation and suppression in the development of lung cancer.
语种	英语
出版者	J BIOL CHEM
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93089]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Wu, Yuan,Feng, Zi-Jie,Gao, Shu-Bin,et al. Interplay between Menin and K-Ras in Regulating Lung Adenocarcinoma[J]. http://dx.doi.org/10.1074/jbc.M112.382416,2012.
APA	Wu, Yuan.,Feng, Zi-Jie.,Gao, Shu-Bin.,Matkar, Smita.,Xu, Bin.,...&金光辉.(2012).Interplay between Menin and K-Ras in Regulating Lung Adenocarcinoma.http://dx.doi.org/10.1074/jbc.M112.382416.
MLA	Wu, Yuan,et al."Interplay between Menin and K-Ras in Regulating Lung Adenocarcinoma".http://dx.doi.org/10.1074/jbc.M112.382416 (2012).