title: Epigenetic alteration of CCDC67 and its tumor suppressor function in gastric cancer.
abstract: In this study, the promoter of the gene coiled-coil domain-containing 67 (CCDC67) was found to be frequently methylated in gastric cancer cell lines and in primary gastric tumors, as examined by restriction landmark genomic scanning. In addition, CCDC67 expression was down-regulated in 72.7% of gastric cancer cell lines tested. In most cases, gene down-regulation was associated with CpG hypermethylation in the CCDC67 promoter. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin A restored CCDC67 expression in down-regulated cell lines. Pyrosequencing analysis of 150 paired primary gastric cancer samples revealed that promoter CpG methylation was increased in 74% of tested tumors compared with paired adjacent normal tissues, and this hypermethylation correlated significantly with down-regulation of CCDC67. CCDC67 protein was localized to the cell membrane by immunocytochemistry. Stable transfection of a CCDC67 gene in one gastric cancer cell line inhibited adhesion-dependent and -independent colony formation, and CCDC67 expression suppressed tumorigenesis in nude mice. We suggest that CCDC67 is a putative tumor suppressor gene that is silenced in gastric cancers by promoter CpG methylation and that it may play an important role in cell signaling and migration related to tumorigenesis.
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Hay-Ran
authors.initials: HR
authors.lastname: Jang
authors.forename: Mirang
authors.initials: M
authors.lastname: Kim
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Oh-Hyung
authors.initials: OH
authors.lastname: Kwon
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Park
authors.forename: Seung-Moo
authors.initials: SM
authors.lastname: Noh
authors.forename: Kyu-Sang
authors.initials: KS
authors.lastname: Song
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Yeul-Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C576056:DEUP1 protein, human; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins