Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 92-kDa type IV collagenase (matrix metalloproteinase-9; MMP-9) is frequently expressed in cells showing an invasive nature during physiological and pathological processes, and the expression is strictly controlled by a variety of trans-membrane signals. Binding sites for NF-kB, Sp-1, and AP-1 are reportedly required for induction of MMP-9 gene expression by tumor necrosis factor-alpha or 12-O-tetradecanoylphorbol-13-acetate. Comparison of the sequence of the newly cloned mouse MMP-9 promoter region with our previous human isolate revealed that, in addition to the above mentioned elements, four units of GGGG(T/A)GGGG sequence (GT box) were conserved between the two species. In this study, we have demonstrated that one of the GT boxes located downstream of the AP-1 site is essential along with the AP-1 site for the activation of the promoter by v-Src but not by tumor necrosis factor-alpha or 12-O-tetradecanoylphorbol-13-acetate. Gel mobility-shift assays revealed that binding proteins for retinoblastoma control element, including Sp-1 family protein, can bind specifically to GT boxes. Thus, the v-Src signals to the AP-1 site and to the GT box homologous to retinoblastoma control element acted synergistically in transcriptional activation. These results suggest that certain v-Src-mediated signals are propagated along pathways that are independent of inflammatory cytokines.
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PMID:v-Src activates the expression of 92-kDa type IV collagenase gene through the AP-1 site and the GT box homologous to retinoblastoma control elements. A mechanism regulating gene expression independent of that by inflammatory cytokines. 822 72

The 92-kDa type IV collagenase (MMP-9) is a metalloproteinase frequently localized in both tumor stroma and in tumor cells, particularly at the tumor invasion front. To explore the factors regulating transcriptional activation of MMP-9 in stromal cells, we used a model system in which fibroblast MMP-9 expression can be upregulated by cell-cell contact with metastatic transformed rat embryo cells. Using transient transfection of reporter gene constructs containing 5'-deleted or mutated MMP-9 promoter fragments, as well as electrophoretic mobility shift assays, the upstream NFkappaB, SP-1, and Ets sites and the downstream AP-1 site and retinoblastoma binding element were shown to be necessary for basal transcriptional activity of fibroblast MMP-9. In contrast only Ets or SP-1 appeared to be involved in contact-mediated induction of MMP-9. Mutation of the upstream AP-1 site increased both basal and contact-stimulated promoter activation. Deletion of the alternating purine-pyrimidine repeat in the downstream promoter decreased transcriptional activity. Together these findings suggest that Ets and SP-1 are the central transcriptional activators of MMP-9 gene expression in fibroblasts specifically responding to tumor cell contact, and that promoter conformation may regulate MMP-9 expression.
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PMID:Tumor cell contact mediated transcriptional activation of the fibroblast matrix metalloproteinase-9 gene: involvement of multiple transcription factors including Ets and an alternating purine-pyrimidine repeat. 951 98

The progression of gliomas has been extensively studied at the genomic level using cDNA microarrays. However, systematic examinations at the protein translational and post-translational levels are far more limited. We constructed a glioma protein lysate array from 82 different primary glioma tissues, and surveyed the expression and phosphorylation of 46 different proteins involved in signaling pathways of cell proliferation, cell survival, apoptosis, angiogenesis, and cell invasion. An analysis algorithm was employed to robustly estimate the protein expressions in these samples. When ranked by their discriminating power to separate 37 glioblastomas (high-grade gliomas) from 45 lower-grade gliomas, the following 12 proteins were identified as the most powerful discriminators: IBalpha, EGFRpTyr845, AKTpThr308, phosphatidylinositol 3-kinase (PI3K), BadpSer136, insulin-like growth factor binding protein (IGFBP) 2, IGFBP5, matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), phosphorylated retinoblastoma protein (pRB), Bcl-2, and c-Abl. Clustering analysis showed a close link between PI3K and AKTpThr308, IGFBP5 and IGFBP2, and IBalpha and EGFRpTyr845. Another cluster includes MMP9, Bcl-2, VEGF, and pRB. These clustering patterns may suggest functional relationships, which warrant further investigation. The marked association of phosphorylation of AKT at Thr308, but not Ser473, with glioblastoma suggests a specific event of PI3K pathway activation in glioma progression.
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PMID:Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays. 1661 7

Recent evidence shows that altered microRNA-9 (miR-9) expression is implicated in the progression of gastric cancer. However, the exact roles and underlying mechanisms of miR-9 in the proliferation, invasion and metastasis of gastric cancer still remain unknown. In this study, miR-9 was found to be down-regulated and inversely correlated with the expression of cyclin D1 and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1) in gastric cancer tissues and cell lines. Bioinformatics analysis revealed the putative miR-9 binding sites in the 3'-untranslated regions (3'-UTR) of cyclin D1 and Ets1 mRNA. Ectopic expression or knockdown of miR-9 resulted in responsively altered expression of cyclin D1, Ets1 and their downstream targets phosphorylated retinoblastoma and matrix metalloproteinase 9 in cultured gastric cancer cell lines SGC-7901 and AGS. In the luciferase reporter system, miR-9 directly targeted the 3'-UTR of cyclin D1 and Ets1, and these effects were abolished by mutating the miR-9 binding sites. Over-expression of miR-9 suppressed the proliferation, invasion, and metastasis of SGC-7901 and AGS cells in vitro and in vivo. Restoration of miR-9-mediated down-regulation of cyclin D1 and Ets1 by transient transfection, rescued the cancer cells from decrease in proliferation, migration and invasion. Furthermore, anti-miR-9 inhibitor promoted the proliferation, migration and invasion of gastric cancer cells, while knocking down of cyclin D1 or Ets1 partially phenocopied the effects of miR-9 over-expression. These data indicate that miR-9 suppresses the expression of cyclin D1 and Ets1 via the binding sites in their 3'-UTR, thus inhibiting the proliferation, invasion and metastasis of gastric cancer.
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PMID:microRNA-9 suppresses the proliferation, invasion and metastasis of gastric cancer cells through targeting cyclin D1 and Ets1. 2338 71