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首页> 外文期刊>Journal of Cellular Physiology >Src oncogene activates MMP-2 expression via the ERK/Sp1 pathway.
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Src oncogene activates MMP-2 expression via the ERK/Sp1 pathway.

机译：Src癌基因激活MMP-2表达式通过

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Previous studies demonstrated that activation of Src oncogene increased matrix metalloproteinase-2 (MMP-2) expression in various types of cells. In this study, we elucidated the underlying mechanism of Src-induced MMP-2. We first used murine fibroblast cell line C3H10T1/2 and its v-Src transfectant IV5 to address this issue. RT-PCR and promoter activity assay indicated that Src stimulated MMP-2 via transcriptional activation. Transfection of constitutively active Src into C3H10T1/2 cells also stimulated MMP-2 mRNA expression. Deletion and mutation analysis indicated that the Sp1 site located within the -91/-84 region of human MMP-2 promoter is the major responsive element for Src. Electrophoresis mobility shift assays showed that Src enhanced the binding of Sp1 to this consensus site to stimulate MMP-2 gene expression. We next investigated the signaling pathway that mediated the effect of Src on MMP-2. Our data showed that extracellular signal-regulated kinase (ERK) pathway inhibitor PD98059, but not the c-Jun N-terminal kinase (JNK) inhibitor SP600125, p38 kinase inhibitor SB203580, and PI3K inhibitor wortmannin, attenuated Src-induced MMP-2 promoter activity. These inhibitors did not show significant effect on basal MMP-2 promoter activity in C3H10T1/2 cells. In addition, the dominant negative mutant of ERK-2 suppressed the activation of MMP-2 by Src. Treatment of PD98059 or an Src specific inhibitor PP1 reduced Sp1 DNA binding activity in IV5 cells. Taken together, our results strongly suggest that Src induces MMP-2 expression via transcription activation and the ERK/Sp1 signaling pathway is involved in this process.
机译：先前的研究表明,激活的Src metalloproteinase-2致癌基因增加矩阵在各种类型的细胞(MMP-2)表达式。这项研究中,我们阐明底层机制Src-induced MMP-2。C3H10T1/2及其小鼠成纤维细胞系v - src转染子IV5来解决这个问题。试验表明,rt - pcr和推广活动Src刺激MMP-2通过转录激活。Src MMP-2 C3H10T1/2细胞也影响了信使rna表达。表明,Sp1站点位于人类MMP-2启动子是-91/-84的地区Src的主要响应要素。化验显示,Src增强流动性转变网站绑定Sp1的共识刺激MMP-2基因表达。调查介导的信号通路MMP-2 Src的效果。细胞外signal-regulated激酶(ERK)通路抑制剂PD98059,但不是c-Jun氨基端激酶抑制剂SP600125(物),人们激酶抑制剂SB203580和PI3K抑制剂渥曼青霉素,减毒Src-induced MMP-2启动子活动。显著影响基底MMP-2启动子在C3H10T1/2细胞活动。显性负突变ERK-2镇压了激活MMP-2 Src。或一个Src特定抑制剂PP1减少Sp1的DNA绑定在IV5细胞活动。我们的研究结果有力地表明,Src诱发MMP-2通过转录激活和表达ERK / Sp1信号通路参与的过程。

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