Evidence for the role of promoter methylation in the regulation of MMP-9 gene expression

被引:77
作者
Chicoine, É [1 ]
Estève, PO [1 ]
Robledo, O [1 ]
Van Themsche, C [1 ]
Potworowski, EF [1 ]
St-Pierre, Y [1 ]
机构
[1] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ H7V 1B7, Canada
关键词
MMP-9; matrix metalloproteinase; DNA methylation; lymphoma; transcription; promoter; zymography; 5-aza-2 '-deoxycytidine; bisulfite;
D O I
10.1016/S0006-291X(02)02283-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several studies have reported that elevated MMP-9 expression in lymphoma tissues correlated with tumor stage, grade, or prognosis. Because the DNA methylation pattern is critical for gene expression, detailed methylation analysis using genomic bisulfite sequencing was performed on a series of lymphoma cell lines. We found an inverse correlation between level of methylation of the MMP-9 promoter and the level of MMP-9 expression. Treating lymphoma cells with a DNA methylation inhibitor decreased MMP-9 promoter methylation and increased MMP-9 messenger RNA and protein secretion. This increased expression was potentiated by PMA, a known stimulus of MMP-9 in lymphoma cells. Finally, experiments using in vitro methylated MMP-9 promoter constructs confirmed the fact that DNA methylation exerts suppression on transcriptional activity. The results thus indicate that methylation may contribute to the transcriptional activity of the MMP-9 promoter. (C) 2002 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:765 / 772
页数:8
相关论文
共 48 条
[1]  
Aoudjit F, 1998, J IMMUNOL, V160, P2967
[2]  
Aoudjit F, 1999, INT J CANCER, V82, P743, DOI 10.1002/(SICI)1097-0215(19990827)82:5<743::AID-IJC19>3.0.CO
[3]  
2-6
[4]  
Baylin SB, 1998, ADV CANCER RES, V72, P141
[5]   Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis [J].
Bergers, G ;
Brekken, R ;
McMahon, G ;
Vu, TH ;
Itoh, T ;
Tamaki, K ;
Tanzawa, K ;
Thorpe, P ;
Itohara, S ;
Werb, Z ;
Hanahan, D .
NATURE CELL BIOLOGY, 2000, 2 (10) :737-744
[6]   DIRECT EVIDENCE LINKING EXPRESSION OF MATRIX METALLOPROTEINASE-9 (92-KDA GELATINASE/COLLAGENASE) TO THE METASTATIC PHENOTYPE IN TRANSFORMED RAT EMBRYO CELLS [J].
BERNHARD, EJ ;
GRUBER, SB ;
MUSCHEL, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (10) :4293-4297
[7]   THE ESSENTIALS OF DNA METHYLATION [J].
BIRD, A .
CELL, 1992, 70 (01) :5-8
[8]   SP1 ELEMENTS PROTECT A CPG ISLAND FROM DE-NOVO METHYLATION [J].
BRANDEIS, M ;
FRANK, D ;
KESHET, I ;
SIEGFRIED, Z ;
MENDELSOHN, M ;
NEMES, A ;
TEMPER, V ;
RAZIN, A ;
CEDAR, H .
NATURE, 1994, 371 (6496) :435-438
[9]   Sp1 binding is inhibited by (m)Cp(m)CpG methylation [J].
Clark, SJ ;
Harrison, J ;
Molloy, PL .
GENE, 1997, 195 (01) :67-71
[10]   Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions [J].
Dubois, B ;
Masure, S ;
Hurtenbach, U ;
Paemen, L ;
Heremans, H ;
van den Oord, J ;
Sciot, R ;
Meinhardt, T ;
Hämmerling, G ;
Opdenakker, G ;
Arnold, B .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (11) :1507-1515