Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer

被引:74
作者
Suzuki, Chie
Takahashi, Koji
Hayama, Satoshi
Ishikavva, Nobuhisa
Kato, Tatsuya
Ito, Tomoo
Tsuchiya, Eiju
Nakamura, Yusuke
Daigo, Yataro
机构
[1] Univ Tokyo, Mol Med Lab, Human Genome Ctr, Inst Med Sci, Tokyo 1088639, Japan
[2] Hokkaido Univ, Dept Surg Pathol, Grad Sch Med, Sapporo, Hokkaido, Japan
[3] Canc Ctr Res Inst, Kanagawa, Japan
关键词
D O I
10.1158/1535-7163.MCT-06-0659
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Through genome-wide expression profile analysis for non small cell lung cancers (NSCLC), we found overexpression of a Myc-associated protein with JmjC domain (MAPJD) gene in the great majority of NSCLC cases. Induction of exogenous expression of MAPJD into NIH3T3 cells conferred growth-promoting activity. Concordantly, in vitro suppression of MAPJD expression with small interfering RNA effectively suppressed growth of NSCLC cells, in which MAPJD was overexpressed. We found four candidate MAPJD target genes, SBNO1, TGFBRAP1, RIOK1, and RASGEF1A, which were the most significantly induced by exogenous MAPJD expression. Through interaction with MYC protein, MAPJD transactivates a set of genes, including kinases and cell signal transducers that are possibly related to proliferation of lung cancer cells. As our data imply that MAPJD is a novel member of the MYC transcriptional complex and its activation is a common feature of lung cancer, selective suppression of this pathway could be a promising therapeutic target for treatment of lung cancers.
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页码:542 / 551
页数:10
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