Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription factor ETS-1 is induced in endothelial cells (ECs) by angiogenic growth factors and the specific elimination of ETS-1 synthesis by antisense oligodeoxynucleotide inhibited angiogenesis in vitro (Iwasaka et al., 1996, J Cell Physiol 169:522-531). To understand the precise role of ETS-1 in angiogenesis, we established both high and low ETS-1 expression EC lines and compared angiogenic properties of these cell lines with those of the parental murine EC line, MSS-31. Although growth rate was almost identical for each cell line, the invasiveness was markedly enhanced in high ETS-1 expression cells and reduced in low ETS-1 expression cells compared with that of parental cells. The gene expressions of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9) and gelatinolytic activity of MMP-9 were significantly increased in high ETS-1 expression cells. Low ETS-1 expression cells could not spread on a vitronectin substratum, and the phosphorylation of focal adhesion kinase was markedly impaired because of the reduced expression of integrin beta3. These results indicate that ETS-1 is a principal regulator that converts ECs to the angiogenic phenotype.
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PMID:ETS-1 converts endothelial cells to the angiogenic phenotype by inducing the expression of matrix metalloproteinases and integrin beta3. 1004 76

Colorectal cancers from the mutator phenotype pathway display distinctive pathological features and confer a lesser aggressiveness than colorectal adenocarcinomas originated by the suppressor pathway. The goal of this work was to test whether tumors developed through the mutator pathway could show a decrease in matrix metalloproteinase (MMP) activity. We evaluated levels and activity of gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as stromelysin-1 (MMP-3) expression in 101 sporadic colorectal tumors in consideration of the microsatellite instability (MSI) status of the groups. Gelatinases were analyzed by ELISA and zymography. The MMP-3 study was performed by real-time quantitative PCR. MMP-9 total levels were significantly higher in MSI-H tumors. However, levels of the active MMP-9 form were significantly much lower in this group of tumors. Data from real-time quantitative PCR indicated that levels of MMP-3 for MSI-L/MSS tumors were much higher as compared with those observed in MSI-H cancers (P = 0.033). Moreover, all MSI-H tumors showed nucleotide insertions and/or deletions in MMP-3 promoter. These mutations were not observed in the group of MSI-L/MSS tumors. Our data indicate that the MMP-3 promoter constitutes a novel target of the defective mismatch repair machinery in sporadic colorectal tumors, resulting in a dramatic decrease in the levels of the active MMP-9 form, which may result in a lessened capacity for invasion.
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PMID:Stromelysin-1 promoter mutations impair gelatinase B activation in high microsatellite instability sporadic colorectal tumors. 1209