Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells

Haw Young Kwon, Seok Jo Kim, Cheorl Ho Kim, Sung Wook Son, Kyoung Sook Kim, Jai Heon Lee, Su Il Do, Young Choon Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

In this study, we have shown that gene expression of human GD3 synthase (hST8Sia I) is suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To elucidate the mechanism underlying the down regulation of hST8Sia I gene expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible promoter region within the hST8Sia I gene using luciferase constructs carrying 5'-deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-k{cyrillic}B, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-k{cyrillic}B binding site at -731 to -722 is crucial for TPL-induced suppression of hST8Sia I in SK-MEL-2 cells. This suggests that TPL induces down-regulation of hST8Sia I gene expression through NF-κB activation in human melanoma cells.

Original languageEnglish (US)
Pages (from-to)849-855
Number of pages7
JournalExperimental and Molecular Medicine
Volume42
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • 8-sialyltransferase
  • Gene expression regulation
  • Melanoma
  • NF-κB
  • Triptolide
  • α-n-acetylneuraminate α-2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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