title: Identification of a nuclear protein, LRRC42, involved in lung carcinogenesis.
abstract: On the basis of the gene expression profiles of 120 lung cancer cases using a cDNA microarray containing 27,648 genes or expressed sequence tags (ESTs), we identified LRRC42 (Leucine-rich repeat containing 42) to be significantly upregulated in the majority of lung cancers. Northern blot analysis demonstrated that LRRC42 was expressed only in testis among normal tissues examined. Knockdown of LRRC42 expression by siRNA against LRRC42 significantly suppressed the growth of lung cancer cells. On the other hand, stable induction of LRRC42 expression significantly promoted cell growth. LRRC42, which was found to localize in the nucleus of mammalian cells, is likely to interact with and stabilize GATAD2B (GATA zinc finger domain-containing 2B) and MBD3 (Methyl-CpG-binding domain protein 3) proteins that could contribute to lung cancer cell proliferation partly through the regulation of p21Waf1/Cip1. Our findings suggest that LRRC42 overexpression as well as its interaction with LRRC42-GATAD2B might play essential roles in lung carcinogenesis, and be a promising molecular target for lung cancer therapy.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujitomo
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Laboratory for Biomarker Development, Center for Genomic Medicine, RIKEN, Yokohama 230-0045, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050980:GATA Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D013737:Testis / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D050980:GATA Transcription Factors; C468770:GATAD2B protein, human; C000594498:LRRC42 protein, human; C115369:MBD3 protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins