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  • 1
    Electronic Resource
    Electronic Resource
    Expression of membrane-type matrix metalloproteinase-1 in human pancreatic adenocarcinomas (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 65-72 
    Details
    ISSN: 1432-1335
    Keywords: Key words Membrane-type matrix metalloproteinase-1 (MT-MMP-1) ; Human pancreatic adenocarcinoma ; Desmoplasia ; Non-radioactive in situ hybridization ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of a new type of matrix metalloproteinase, membrane-type matrix metalloproteinase-1 (MT-MMP-1), was examined in 24 cases of primary pancreatic adenocarcinomas and 9 cases of secondary liver tumors derived from pancreatic adenocarcinomas, using a non-radioactive in situ hybridization and immunohistochemical methods. Out of 24 cases of primary pancreatic adenocarcinomas, 18 showed positive expression of MT-MMP-1 transcripts in cancer cells and 20 of 24 showed positive expression in the tumor stromal cells. The immunoreactivity of the gene products for MT-MMP-1 was demonstrated to be almost the same, as shown by in situ hybridization in these 24 cases. In particular, both the staining intensity for MT-MMP-1 transcripts and the immunoreactivity of the gene products in the tumor stromal cells of mucinous cystadenocarcinomas were significantly weaker than those of common-type ductal adenocarcinomas among the 24 cases. All of the 9 cases of secondary liver tumors derived from pancreatic adenocarcinomas showed positive expression for MT-MMP-1 transcripts but less immunoreactivity for the gene products. These results suggest that MT-MMP-1 is transcribed and translated in both cancer cells and the tumor stromal cells in human pancreatic adenocarcinomas. Furthermore, considering that common-type ductal adenocarcinoma of the pancreas usually shows a strong desmoplastic reaction, while mucinous cystadenocarcinoma typically does not, MT-MMP-1 expressed in the tumor stromal cells of common-type adenocarcinomas may be involved in processes leading to the desmoplastic reaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050137
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Elevated cyclic AMP suppresses ConA-induced MT1-MMP expression in MDA-MB-231 human breast cancer cells (1998)
    Springer
    Clinical & experimental metastasis 16 (1998), S. 185-191 
    Details
    ISSN: 1573-7276
    Keywords: activation ; cAMP ; Concanavalin A ; gelatinase A ; human breast cancer ; MT-MMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported that induction of MMP-2 activation by Concanavalin A (ConA) in MDA-MB-231human breast cancer cells involves both transcriptional and post-transcriptional mechanisms, and that the continuous presence of ConA is required for MMP-2 activation (Yu et al. Cancer Res, 55, 3272-7, 1995).In an effort to identify signal transduction pathways which may either contribute to or modulate this mechanism,we found that three different cAMP-inducing agents, cholera toxin (CT), forskolin (FSK), and3-isobutyl-1-methylxanthine (IBMX) partially inhibited ConA-induced MT1-MMP expression and MMP-2activation in MDA-MB-231 cells. Combinations of CT or FSK with IBMX exhibited additive effects on reduction of MT1-MMP mRNA expression and MMP-2 activation. Agents which increase cAMP levels appeared to target transcriptional aspects of ConA induction, reducing MT1-MMP mRNA and protein in parallel with the reduced MMP-2 activation. In the absence of ConA, down-regulation of constitutive production of MT1-MMP mRNA and protein was observed, indicating that cAMP acts independently of ConA. These observations may help to elucidate factors regulating MT1-MMP expression, which may be pivotal to the elaboration of invasive machinery on the cell surface. © Rapid Science 1998
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006580406314
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