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Glycobiology Advance Access originally published online on October 27, 2007
Glycobiology 2008 18(1):104-113; doi:10.1093/glycob/cwm120
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Expression of the Human Sda β-1,4-N-Acetylgalactosaminyltransferase II Gene is Dependent on the Promoter Methylation Status

Hou-Ren Wang2,3, Chuang-Yi Hsieh3, Yuh-Ching Twu3 and Lung-Chih Yu1,2,3

2 Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan
3 Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan

1 To whom correspondence should be addressed: Tel: +886-2-3366-4070; Fax: +886-2-2363-5038; e-mail: yulc{at}ntu.edu.tw

Received on August 22, 2007; revised on October 16, 2007; accepted on October 20, 2007

It has been noted that the expression of Sda, including its antigenic structure, the β-1,4-N-acetylgalactosyltransferase II (β4GalNAcT-II) activity responsible for its formation, and the Sda β4GalNAcT-II mRNA transcript, is drastically reduced in oncogenetic processes in gastrointestinal tissues. Markedly reduced metastatic potential has been demonstrated in colon and gastric cancer cells transfected with the Sda β4GalNAcT-II gene. In this study, a putative CpG island encompassing the promoter and exon 1 regions in the human Sda β4GalNAcT-II gene was identified, and the investigation of DNA methylation of the Sda gene promoter region demonstrated a clear association between the methylation status of the CpG island promoter and expression of the Sda gene in gastrointestinal cancer cell lines. Hypomethylation of the promoter region of the Sda gene was shown in cells where this gene was expressed. By contrast, there was significant hypermethylation of the Sda gene promoter in cells that did not express the gene. A specific methylation profile in the Sda gene CpG island was demonstrated in KATO III gastric cancer cells. In colon cancer cells with the hypermethylated Sda gene promoter, treatment with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine, resulted in demethylation of the promoter region and substantially induced the expression of the Sda gene and the Sda antigenic structure. These results strongly suggest that promoter DNA methylation plays a crucial role in the regulation of the Sda β4GalNAcT-II gene and Sda antigen expression.

Key words: DNA methylation / gastrointestinal cancers / gene expression / N-acetylgalactosaminyltransferase / Sda antigen


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