Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascades

被引:49
作者
Lakka, SS
Jasti, SL
Kyritsis, AP
Yung, WKA
Ali-Osman, F
Nicolson, GL
Rao, JS
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA
[3] Inst Mol Med, Huntington Beach, CA USA
关键词
MMP-9; type IV collagenase; glioblastoma; JNK; ERK;
D O I
10.1023/A:1006724826083
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Our previous studies have shown that MMP-9 levels are significantly elevated during the progression of human gliomas. In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which JNK/ERK1 is constitutively activated. SNB19 cells that were transfected with dominant-negative JNK, MEKK, and ERK1 expression vectors showed reduced MMP-9 promoter activity. In addition, conditioned medium collected from SNB19 cells transfected with these expression vectors showed diminished MMP-9 activity in the presence of phorbol myristate acetate, as determined by gelatin zymography. The cotransfection of SNB19 cells with kinase-deficient c-raf also diminished MMP-9 promoter activity. Further, in the presence of a specific inhibitor of MEKK (PD098059), the Matrigel invasion assay showed the invasiveness of dominant-negative SNB19 cells transfected with dominant-negative JNK1 or ERK1 to be remarkably reduced. In conclusion, our studies showed for the first time that MMP-9 production and the invasive behavior of SNB19 cells are regulated by JNK- and ERK-dependent signaling modules and that interfering with either of the pathways reduces invasiveness.
引用
收藏
页码:245 / 252
页数:8
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