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KMID : 0620920100420120849
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Experimental & Molecular Medicine
2010 Volume.42 No. 12 p.849 ~ p.855
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Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells
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Kwon Haw-Young
Kim Seok-Jo
Kim Cheorl-Ho
Son Sung-Wook
Kim Kyoung-Sook
Lee Jai-Heon
Do Su-Il
Lee Young-Choon
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Abstract
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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-κB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-κB 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.
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KEYWORD
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α -N-acetylneuraminate α -2, 8-sialyltransferase, expression regulation, melanoma, NF-κ B, triptolide
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