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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.
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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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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