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

Chie Suzuki; Koji Takahashi; Satoshi Hayama; Nobuhisa Ishikawa; Tatsuya Kato; Tomoo Ito; Eiju Tsuchiya; Yusuke Nakamura; Yataro Daigo

doi:10.1158/1535-7163.MCT-06-0659

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

Mol Cancer Ther. 2007 Feb;6(2):542-51. doi: 10.1158/1535-7163.MCT-06-0659.

Authors

Chie Suzuki¹, Koji Takahashi, Satoshi Hayama, Nobuhisa Ishikawa, Tatsuya Kato, Tomoo Ito, Eiju Tsuchiya, Yusuke Nakamura, Yataro Daigo

Affiliation

¹ 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.

PMID: 17308053
DOI: 10.1158/1535-7163.MCT-06-0659

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.

MeSH terms

Animals
Blotting, Northern
Blotting, Western
Carcinoma, Non-Small-Cell Lung / metabolism*
Carcinoma, Non-Small-Cell Lung / pathology
Cell Transformation, Neoplastic
Cells, Cultured
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Flow Cytometry
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Immunoenzyme Techniques
Immunoprecipitation
Intracellular Signaling Peptides and Proteins / metabolism
Lung / metabolism
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Mice
NIH 3T3 Cells
Nuclear Proteins / physiology*
Oligonucleotide Array Sequence Analysis
Oncogene Proteins / physiology*
Oncogenes / physiology*
Prognosis
Proto-Oncogene Proteins c-myc / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Tissue Array Analysis
ras Guanine Nucleotide Exchange Factors / metabolism

Substances

Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Oncogene Proteins
Proto-Oncogene Proteins c-myc
RASGEF1A protein, human
RNA, Messenger
RNA, Small Interfering
TGFBRAP1 protein, human
ras Guanine Nucleotide Exchange Factors