https://scholars.lib.ntu.edu.tw/handle/123456789/456375
標題: | Bone morphogenetic protein-2 enhances the motility of chondrosarcoma cells via activation of matrix metalloproteinase-13 | 作者: | CHUN-HAN HOU Hsiao Y.-C. Fong Y.-C. Tang C.-H. |
公開日期: | 2009 | 卷: | 44 | 期: | 2 | 起(迄)頁: | 233-242 | 來源出版物: | Bone | 摘要: | Chondrosarcoma is a low-grade sarcoma characterized by developing metastases and high local recurrence rate. Bone morphogenetic protein-2 (BMP-2) plays an essential role in tumor progression and metastasis. Here we found that BMP-2 induced the migration of human chondrosarcoma cells (JJ012 cells). BMP-2 also increased the secretion of metalloproteinase-13 (MMP-13) in JJ012 cells, as shown by reverse transcriptase-polymerase chain reaction, western blot and zymographic analysis. The MMP-13 small interfering RNA inhibited the BMP-2-induced MMP-13 expression and thereby significantly inhibited the BMP-2-induced cell migration. Furthermore, phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002) or Akt inhibitor suppressed BMP-2-induced MMP-13 mRNA expression. Transient transfection with dominant negative p85 and Akt mutant also showed that the PI3K/Akt signaling pathway was involved in BMP-2-induced MMP-13 expression. In addition, AP-1 decoy oligodeoxynucleotide also suppressed the MMP-13 promoter activity enhanced by BMP-2. Moreover, BMP-2 increased the binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter. Taken together, our results indicated that BMP-2 enhanced the invasiveness of chondrosarcoma cells by increasing MMP-13 expression through the PI3K, Akt, c-Fos/c-Jun and AP-1 signal transduction pathway. ? 2008 Elsevier Inc. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-58249098395&doi=10.1016%2fj.bone.2008.09.021&partnerID=40&md5=c3a63bc6ad154589e00d3cd41c51b6d3 https://scholars.lib.ntu.edu.tw/handle/123456789/456375 |
ISSN: | 8756-3282 | DOI: | 10.1016/j.bone.2008.09.021 | SDG/關鍵字: | 2 morpholino 8 phenylchromone; bone morphogenetic protein; bone morphogenic protein 2; collagenase 3; messenger RNA; phosphatidylinositol 3 kinase inhibitor; protein c jun; protein kinase B; protein kinase B inhibitor; protein p85; small interfering RNA; transcription factor AP 1; unclassified drug; article; cancer cell; cell migration; cell motility; chondrosarcoma; controlled study; enzyme activation; enzyme release; human; human cell; oncogene c fos; protein expression; reverse transcription polymerase chain reaction; signal transduction; transient transfection; Western blotting; zymography; 1-Phosphatidylinositol 3-Kinase; Bone Morphogenetic Protein 2; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Chondrosarcoma; Enzyme Activation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 13; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Signal Transduction; Time Factors; Transcription Factor AP-1; Up-Regulation |
顯示於: | 醫學系 |
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