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Glycobiology Advance Access published online on October 27, 2007
Glycobiology, 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 Human Sda ß-1,4-N-Acetylgalactosaminyltransferase II Gene is Dependent on 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; Institute of Biochemical Sciences, National Taiwan University, P.O. Box 23-106, Taipei 106, Taiwan Tel: +886-2-3366-4070; Fax: +886-2-2363-5038; e-mail: yulc{at}ntu.edu.tw

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

It has been noted that the expression of Sda, including its antigenic structure, the ß-1,4-N-acetylgalactosyltransferase II (ß4GalNAcT-II) activity responsible for its formation, and the Sda ß4GalNAcT-II mRNA transcript, are drastically reduced in oncogenetic processes in gastrointestinal tissues. Markedly reduce metastatic potential has been demonstrated in colon and gastric cancer cells transfected with the Sda ß4GalNAcT-II gene. In this study, a putative CpG island encompassing the promoter and exon 1 regions in the human Sda ß4GalNAcT-II gene was identified, and the investigation of DNA methylation of the Sda gene promoter region demonstrated a clear association between 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 regulation of the Sda ß4GalNAcT-II gene and Sda antigen expression.

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


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