Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells
Experimental & Molecular Medicine
;
: 849-855, 2010.
Article
in English
| WPRIM
| ID: wpr-122573
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 downregulation 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-kappaB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-kappaB 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-kappaB activation in human melanoma cells.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phenanthrenes
/
Sialyltransferases
/
Tumor Cells, Cultured
/
Down-Regulation
/
NF-kappa B
/
Promoter Regions, Genetic
/
Genes, Reporter
/
Cell Proliferation
/
Diterpenes
/
Epoxy Compounds
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2010
Type:
Article
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