5-Aza-2′-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating β-galactoside:α2,3-sialyltransferase 6 gene

Vishwanath B. Chachadi, Helen Cheng, David L Klinkebiel, Judith K. Christman, Pi-Wan Cheng

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Sialyl Lewis X is a tumor-associated antigen frequently found in the advanced cancers. However, the mechanism for the production of this cancer antigen is not entirely clear. The objective of this study is to examine whether epigenetics is involved in the regulation of the formation of this antigen. We observed an increase of sialyl Lewis X in HCT15 cells, a colon cancer cell line, treated with 5-Aza-2′-deoxycytidine. This treatment enhanced the expression of β-galactoside:α2,3-sialyltransferase 6 gene and sialyl Lewis X on MUC1, and the adherence of these cells to E-selectin under dynamic flow conditions. In addition, 5-Aza-2′-deoxycytidine treatment inhibited methylation of β-galactoside:α2,3-sialyltransferase 6 gene and siRNA knockdown of this gene drastically reduced sialyl Lewis X without affecting MUC1 expression. We conclude that 5-Aza-2′-deoxycytidine treatment increases sialyl Lewis X on MUC1 by stimulating the β-galactoside:α2,3- sialyltransferase 6 gene via inhibition of DNA methylation. Increased sialyl Lewis X by 5-Aza-2′-deoxycytidine raises a concern about the safety of this chemotherapeutic drug. In addition, β-galactoside:α2,3- sialyltransferase 6 gene may be a potential therapeutic target for suppressing tumorigenicity of colon cancer.

Original languageEnglish (US)
Pages (from-to)586-593
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume43
Issue number4
DOIs
StatePublished - Apr 1 2011

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decitabine
Sialyltransferases
Galactosides
Genes
Colonic Neoplasms
Antigens
Gene Knockdown Techniques
E-Selectin
Neoplasm Antigens
DNA Methylation
Epigenomics
Methylation
Small Interfering RNA
Neoplasms
Tumors
Safety
Cell Line
Cells
Pharmaceutical Preparations

Keywords

  • 5-Aza-2′- deoxycytidine
  • Cancer metastasis
  • Epigenetic regulation of glycosyltransferase gene expression
  • Mucin biosynthesis
  • sLe

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

5-Aza-2′-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating β-galactoside:α2,3-sialyltransferase 6 gene. / Chachadi, Vishwanath B.; Cheng, Helen; Klinkebiel, David L; Christman, Judith K.; Cheng, Pi-Wan.

In: International Journal of Biochemistry and Cell Biology, Vol. 43, No. 4, 01.04.2011, p. 586-593.

Research output: Contribution to journalArticle

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