This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yanagawa, N. Articles by Motoyama, T. Search for Related Content PubMed PubMed Citation Articles by Yanagawa, N. Articles by Motoyama, T.

Demethylation of the Synuclein Gene CpG Island in Primary Gastric Cancers and Gastric Cancer Cell Lines

¹ Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan, and ² Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland

Purpose: Whereas synuclein (SNCG) gene expression is usually highly tissue-specific and restricted to the nervous system, SNCG is expressed in advanced-stage breast and ovarian cancers. When overexpressed, SNCG stimulates cancer cell proliferation and metastasis. It is thought that the molecular mechanism of CpG island demethylation may underlie aberrant SNCG expression. To determine whether aberrant SNCG expression and demethylation play a role in gastric carcinogenesis, we examined the expression and methylation status of SNCG in primary gastric cancers, gastric cancer cell lines, and non-neoplastic gastric mucosal tissues.

Experimental Design: Ten gastric cancer cell lines, 105 primary gastric cancers, and 10 non-neoplastic gastric mucosal tissues were examined. SNCG expression and methylation status were examined by reverse transcription-PCR and bisulfite-single-strand conformational polymorphism followed by direct sequencing, respectively. The relationship between SNCG methylation status and various clinicopathological factors of the primary gastric cancers was then analyzed.

Results: SNCG mRNA expression was observed in 5 of 10 cell lines. Analysis of cell lines positive for SNCG expression revealed that most of the SNCG CpGs were demethylated. SNCG mRNA was not expressed in the 10 non-neoplastic gastric mucosal tissues, although several CpGs were demethylated. Of the 105 primary gastric cancers, 40 (38.1%) showed apparent SNCG demethylation, similar to the result obtained using cell lines. SNCG demethylation was more frequent in primary gastric cancers positive for lymph node metastasis (51%; 26 of 51) than in cancers without lymph node involvement (26%; 14 of 54; P < 0.05), and also more common in stage II-IV (48%; 27 of 56) than in stage I (27%; 13 of 49) cancers (P < 0.05).

Conclusions: Aberrant SNCG gene expression can occur via CpG island demethylation, and tends to occur during the more progressive stages of gastric carcinogenesis.

This article has been cited by other articles:

				M. Ahmad, S. Attoub, M. N. Singh, F. L. Martin, and O. M. A. El-Agnaf {gamma}-Synuclein and the progression of cancer FASEB J, November 1, 2007; 21(13): 3419 - 3430. [Abstract] [Full Text] [PDF]

				Y. Nakamura, F. Tanaka, H. Nagahara, K. Ieta, N. Haraguchi, K. Mimori, A. Sasaki, H. Inoue, K. Yanaga, and M. Mori Opa Interacting Protein 5 (OIP5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer Ann. Surg. Oncol., February 1, 2007; 14(2): 885 - 892. [Abstract] [Full Text] [PDF]

				H. Liu, W. Liu, Y. Wu, Y. Zhou, R. Xue, C. Luo, L. Wang, W. Zhao, J.-D. Jiang, and J. Liu Loss of Epigenetic Control of Synuclein-{gamma} Gene as a Molecular Indicator of Metastasis in a Wide Range of Human Cancers Cancer Res., September 1, 2005; 65(17): 7635 - 7643. [Abstract] [Full Text] [PDF]