アブストラクト(32巻2号:The Bulletin of Kanagawa Dental College)

The Bulletin of Kanagawa Dental College

English

Title : Extracellular Acidic pH and Hypoxia Regulate Expression of Metastasis-related Genes through Independent Mechanism
Subtitle : Selective Proceedings of 38th General Meeting of Kanagawa Odontological Society, 2003
Authors : Yasumasa Kato1, Shigeyuki Ozawa2, Shinri Koshika3, Eiro Kubota2,4, Ryu-Ichiro Hata1,4
Authors(kana) :
Organization : 1Department of Biochemistry and Molecular Biology Kanagawa Dental College, 2Department of Oral and Maxillofacial Surgery Kanagawa Dental College, 3Department of Nutritional Science and Metabolism Kanagawa Dental College, 4Research Center of Advanced Technology for Craniomandibular Function Kanagawa Dental College
Journal : The Bulletin of Kanagawa Dental College
Volume : 32
Number : 2
Page : 117-119
Year/Month : 2004 / 9
Article : Report
Publisher : Kanagawa Odontological Society
Abstract : Extracellular pH (pHe) of tumor tissues is often acidic. We have found that matrix metalloproteinase-9 (MMP-9), which is implicated in tumor invasion and metastasis, is induced by acidic culture medium (pH 5.4-6.5) in mouse B16 melanoma cell clones. Using cDNA microarray, we examined low pHe-induced genes in B16-BL6 cells, in addition to MMP-9. It was found that 25 genes were up-regulated more than 2-fold and 38 genes were down-regulated less than 0.5-fold by acidic pHe. Semi-quantitative reverse transcription-polymerase chain reaction showed increase in MMP-9, MMP-11, angiopoietin-2, vascular endothelial cell growth factor B and C. Expression of these gene was not affected by hypoxia. Interestingly, expression of hypoxia inducible factor 1α was induced by acidic pHe but steady state level of vascular endothelial growth factor A, which is a target gene of hypoxia inducible factor 1α, was unchanged by acidic pHe. Finally, we found significant increase in NFкB activity at acidic pHe. Together, acidic pHe is a microenvironmental factor for tumor cells to regulate metastatic phenotype through NFкB activation independent of hypoxia.
Practice : Dentistry
Keywords : extracellular acidic pH, hypoxia, cDNA microarray, HIF1α, NFкB