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Research Articles: Therapeutics, Targets, and Development

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

¹ Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; ² Department of Surgical Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and ³ Kanagawa Cancer Center Research Institute, Kanagawa, Japan

Requests for reprints: Yataro Daigo, Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ward, Tokyo 108-8639, Japan. Phone: 81-3-5449-5457; Fax: 81-3-5449-5406. E-mail: ydaigo@ims.u-tokyo.ac.jp

Abstract

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. [Mol Cancer Ther 2007;6(2):542–51]

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Received 10/25/06; revised 11/20/06; accepted 12/21/06.

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