RRC ID 77108
著者 Yamanegi K, Yamane J, Kobayashi K, Ohyama H, Nakasho K, Yamada N, Hata M, Fukunaga S, Futani H, Okamura H, Terada N.
タイトル Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells.
ジャーナル Oncol Rep
Abstract Valproic acid, a histone deacetylase inhibitor, increases the expression of cell surface MHC class I-related chain molecules (MICs) A and B (MICA and B) in osteosarcoma cells and decreases their secretion of soluble MICA and MICB, which are produced by the proteolytic cleavage of cell surface MICs. Osteosarcoma cells have been reported to produce high levels of matrix metalloproteinase (MMP)-2 and -9. In this study, we investigated the involvement of MMP-2 and -9 in the inhibitory action of valproic acid (VPA) on the proteolytic cleavage of cell surface MICs using the U-2 OS and SaOS-2 osteosarcoma cell lines. VPA caused a marked decrease in the expression of MMP-9 mRNA in the U-2 OS and SaOS-2 cells and in the expression of MMP-2 mRNA in the U-2 OS cells, but only a slight decrease in the expression of MMP-2 mRNA in the SaOS-2 cells. The transfection of small interfering RNA (siRNA) for MMP-9 decreased the secretion of soluble MICA and MICB by both U-2 OS and SaOS-2 cells, but that of siRNA for MMP-2 did not. The present study therefore demonstrates that the downregulation of MMP-9 mRNA by VPA plays a role in the inhibitory action of VPA on the secretion of soluble MICA and MICB in osteosarcoma cells.
巻・号 28(5)
ページ 1585-90
公開日 2012-11-1
DOI 10.3892/or.2012.1981
PMID 22923031
MeSH Bone Neoplasms / genetics Bone Neoplasms / metabolism Cell Line, Tumor Dipeptides / pharmacology Down-Regulation Histocompatibility Antigens Class I / biosynthesis* Humans Matrix Metalloproteinase 2 / biosynthesis Matrix Metalloproteinase 2 / genetics* Matrix Metalloproteinase 9 / biosynthesis Matrix Metalloproteinase 9 / genetics* Membrane Proteins / biosynthesis Osteosarcoma / genetics* Osteosarcoma / metabolism RNA Interference RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering Valproic Acid / pharmacology*
IF 3.417
リソース情報
ヒト・動物細胞 Saos-2(RCB0428)