Epigenetic alteration of CCDC67 and its tumor suppressor function in gastric cancer

Sung Joon Park, Hay Ran Jang, Mirang Kim, Jeong Hwan Kim, Oh Hyung Kwon, Jong Lyul Park, Seung Moo Noh, Kyu Sang Song, Seon Young Kim, Yeul Hong Kim, Yong Sung Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1494-1501
Number of pages8
JournalCarcinogenesis
Volume33
Issue number8
DOIs
Publication statusPublished - 2012 Aug 1

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Epigenomics
Stomach Neoplasms
Cell Line
decitabine
Neoplasms
Methylation
trichostatin A
Carcinogenesis
Down-Regulation
Genes
Tumor Suppressor Genes
Nude Mice
Cell Movement
Transfection
Stomach
Immunohistochemistry
Cell Membrane
Proteins
Therapeutics

ASJC Scopus subject areas

  • Cancer Research

Cite this

Park, S. J., Jang, H. R., Kim, M., Kim, J. H., Kwon, O. H., Park, J. L., ... Kim, Y. S. (2012). Epigenetic alteration of CCDC67 and its tumor suppressor function in gastric cancer. Carcinogenesis, 33(8), 1494-1501. https://doi.org/10.1093/carcin/bgs178

Epigenetic alteration of CCDC67 and its tumor suppressor function in gastric cancer. / Park, Sung Joon; Jang, Hay Ran; Kim, Mirang; Kim, Jeong Hwan; Kwon, Oh Hyung; Park, Jong Lyul; Noh, Seung Moo; Song, Kyu Sang; Kim, Seon Young; Kim, Yeul Hong; Kim, Yong Sung.

In: Carcinogenesis, Vol. 33, No. 8, 01.08.2012, p. 1494-1501.

Research output: Contribution to journalArticle

Park, SJ, Jang, HR, Kim, M, Kim, JH, Kwon, OH, Park, JL, Noh, SM, Song, KS, Kim, SY, Kim, YH & Kim, YS 2012, 'Epigenetic alteration of CCDC67 and its tumor suppressor function in gastric cancer', Carcinogenesis, vol. 33, no. 8, pp. 1494-1501. https://doi.org/10.1093/carcin/bgs178
Park, Sung Joon ; Jang, Hay Ran ; Kim, Mirang ; Kim, Jeong Hwan ; Kwon, Oh Hyung ; Park, Jong Lyul ; Noh, Seung Moo ; Song, Kyu Sang ; Kim, Seon Young ; Kim, Yeul Hong ; Kim, Yong Sung. / Epigenetic alteration of CCDC67 and its tumor suppressor function in gastric cancer. In: Carcinogenesis. 2012 ; Vol. 33, No. 8. pp. 1494-1501.
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