アブストラクト（30巻1号：The Bulletin of Kanagawa Dental College）

The Bulletin of Kanagawa Dental College

English

Title　： Rho A -> phospholipase D -> p38 MAP kinase signaling is an extracellular low pH responsible pathway for matrix metalloproteinase-9 expression in mouse metastatic melanoma cells.
Subtitle　： Selective Proceedings of 36th General Meeting of Kanagawa Odontological Society, 2001
Authors　： Yasumasa Kato1, Shinri Koshika1, Ryu-Ichiro Hata1,2
Authors（kana）　：
Organization　： 1Department of Biochemistry and Molecular Biology, 2Division of Gene Regulation, Bioventure Research Center, Kanagawa Dental College
Journal　： The Bulletin of Kanagawa Dental College
Volume　： 30
Number　： 1
Page　： 73-75
Year/Month　： 2002 / 3
Article　： Report
Publisher　： Kanagawa Odontological Society
Abstract　： Extracellular pH (pHe) of tumor tissue is well known to be acidic. Matrix metalloproteinase-9 (MMP-9)/gelatinase B, which is one of the key enzymes for extracellular matrix degradation during tumor invasion and metastasis, was found to be induced by acidic microenvironments. In this study, we examined the signaling pathway for low pHe to induce MMP-9 expression in mouse metastatic B16 melanoma cells. MMP-9 expression was inhibited by 1-butanol (an inhibitor of phospholipase D (PLD)), suggesting that PLD contributed to the MMP-9 induction by low pHe. Indeed, PLD activity was 5 times higher in the cells cultured in low pH than in the neutral pH, and the high levels of PLD activity was observed 6 h after pH shift to acidic and prolonged at least until 24 h. Furthermore, exogenous PLD induced MMP-9 expression in the cells cultured in the neutral pH. On the other hand, C3 exoenzyme (an inhibitor of Rho A) inhibited MMP-9 expression in low pHe and transfection of RhoA induced MMP-9 expression in the cultures with neutral pH. In addition, it was observed that SB20358, a p38 mitogen activated protein (MAP) kinase specific inhibitor, significantly inhibited MMP-9 expression, and that p38 MAP kinase was activated gradually from 6h to 24 h after pH shift to acidic. From these results, RhoA -> PLD -> p38 MAP kinase pathway was thought to be a low pHe responsible pathway for the MMP-9 expression.
Practice　： Dentistry
Keywords　： Matrix metalloproteinases, Extracellular low pH, Rho A, Phospholipase D