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  • 1
    Electronic Resource
    Electronic Resource
    Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in metastatic MDCK cells transformed by v-src (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 105-110 
    Details
    ISSN: 1573-7276
    Keywords: matrix metalloproteinase ; MDCK cells ; metastasis ; MT1-MMP ; TIMP-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article discusses the transformation of epithelial Madin-Durby canine kidney (MDCK) cells with v-src induced expression of membrane-type 1-matrix metalloproteinase (MT1-MMP) and metastatic growth in nude mice (Kadono Y et al., Cancer Res 1998; 58: 2240–44). To analyze genes associated with invasive phenotype of v-src MDCK cells, mRNA differential display was performed between control and the transformed cells. A clone 12′, the expression of which was clearly up-regulated in the transformed cells, encoded a protein 81% homologous to human tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Northern hybridization showed that only MT1-MMP expression was enhanced and other matrix metalloproteinases (MMPs) were undetectable or rather repressed in the transformed cells. Proteolytic activity against type I gelatin was observed in v-src MDCK cells, which was inhibited only by TIMP-2 but not by TIMP-1. MDCK cells stably transfected with the MT1-MMP gene also degraded gelatin, which was selectively inhibited by TIMP-2. These results suggest that MT1-MMP, the expression of which is induced in v-src MDCK cells, degrades extracellullar matrix by itself rather than through the activation of progelatinase A, which in turn contributes to the metastasis of the transformed cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006596620406
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  • 2
    Electronic Resource
    Electronic Resource
    Induction of membrane-type matrix metalloproteinase-1 stimulates angiogenic activities of bovine aortic endothelial cells (1999)
    Springer
    Angiogenesis 3 (1999), S. 167-174 
    Details
    ISSN: 1573-7209
    Keywords: angiogenesis ; bovine aortic endothelial cells ; MMP-2 ; MT1-MMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Matrix metalloproteinases (MMPs) have been reported to play critical roles in endothelial cell migration and matrix remodeling during the angiogenic process. Among these MMPs, membrane-type MMP-1 (MT1-MMP) is an important molecule that can trigger the invasion of tumor cells by activating MMP-2 on their plasma membrane. However, the precise involvement of MT1-MMP in the angiogenic process has not been determined. To investigate the roles of the MT1-MMP by the matrix remodeling of endothelial cells, MT1-MMP expression vector was transfected into bovine aortic endothelial cells (BAECs). Increased expression of MT1-MMP in BAECs enhanced the activation of MMP-2, invasion and migration of BAECs. Moreover, the capacity of tube formation was increased in MT1-MMP transfectants. However, cotransfection with antisense MT1-MMP expression vector abolished the effects of MT1-MMP overexpression. These observations indicate that MT1-MMP is involved in the angiogenic process of endothelial cells in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009065709676
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  • 3
    Electronic Resource
    Electronic Resource
    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 (1998)
    Springer
    Clinical & experimental metastasis 16 (1998), S. 169-177 
    Details
    ISSN: 1573-7276
    Keywords: cell-cell contact ; meyalloproteinases ; metastasis ; transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 NFκB, 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 fibro-blast 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. © Rapid Science 1998
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006576305405
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