tris(2-pyridylmethyl)amine and Colonic-Neoplasms

tris(2-pyridylmethyl)amine has been researched along with Colonic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for tris(2-pyridylmethyl)amine and Colonic-Neoplasms

ArticleYear
Epidermal growth factor upregulates matrix metalloproteinase-7 expression through activation of PEA3 transcription factors.
    International journal of oncology, 2004, Volume: 24, Issue:6

    MMP-7 is a member of the matrix metalloproteinase family and has been shown to be involved in early intestinal tumorigenesis. However, the factors which regulate MMP-7 gene transcription in the context of early colon cancer remain to be elucidated. Epidermal growth factor (EGF) and the EGF receptor have also been demonstrated to be important in the establishment of colon adenomas. We were therefore interested in addressing the question of whether MMP-7 could be regulated by EGF and in identifying the molecular mechanisms through which this process occurs. Herein, we have demonstrated that EGF enhanced the endogenous expression of MMP-7 in a number of human colon cancer cell lines. Analysis of the MMP-7 promoter sequence reveals the presence of a number of transcription factor binding sites including ETS and AP-1 sites. Results using PEA3, ETS and AP-1 artificial promoters showed that EGF enhanced PEA3 transcription factor activity by up to 70% in comparison to non-treated cell lines. Western blot analysis of nuclear extracts from EGF stimulated cells demonstrated that there was an increase in PEA3 protein when compared to non-treated cells. In addition, using a MAPK inhibitor we have shown that EGF can mediate this increase in PEA3 transcription factors via the MAPK pathway. Using EMSA analysis we also observed that the EGF stimulated increase in PEA3 transcription factors led to increased binding to specific ETS sites within the MMP-7 promoter. These data demonstrate for the first time that EGF directly enhances MMP-7 expression via the activation of PEA3 transcription factors.

    Topics: Binding Sites; Blotting, Western; Cell Nucleus; Colonic Neoplasms; Electrophoretic Mobility Shift Assay; Enzyme Inhibitors; Epidermal Growth Factor; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 7; Mitogen-Activated Protein Kinase Kinases; Promoter Regions, Genetic; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ets; Pyridines; Regulatory Sequences, Nucleic Acid; Transcription Factor AP-1; Transcription Factors; Tumor Cells, Cultured; Up-Regulation

2004
Protein kinase C inhibition induces DNA fragmentation in COLO 205 cells which is blocked by cysteine protease inhibition but not mediated through caspase-3.
    Experimental cell research, 2003, Sep-10, Volume: 289, Issue:1

    Enhancing apoptosis to remove abnormal cells has potential in reversing cancerous processes. Caspase-3 activation generally accompanies apoptosis and its substrates include enzymes responsible for DNA fragmentation and isozymes of protein kinase C (PKC). Recent data, however, question its obligatory role in apoptosis. We have examined whether modulation of PKC activity induces apoptosis in COLO 205 cells and the role of caspase-3. Proliferation ([3H]thymidine) and apoptosis (DNA fragmentation and FACS) of COLO 205 cells were measured in response to PKC activation and inhibition. Caspase-3 activity was assayed and the effects of its inhibition with Ac-DEVD-cmk, and the effect of other protease inhibitors, on apoptosis were determined. PKC activation and inhibition both reduced DNA synthesis and induced DNA fragmentation. As PKC inhibitors induced DNA fragmentation more rapidly than PKC activators and failed to block activator effects, we conclude that it is PKC down-regulation (i.e., inhibition) after activator exposure that mediates apoptosis. Increases in caspase-3 activity occurred during apoptosis but apoptosis was not blocked by caspase inhibition. By contrast, the cysteine protease inhibitor, E-64d, blocked apoptosis. Cysteine proteases not of the caspase family may either act more closely to the apoptotic process than caspases or lie on an alternative, more active pathway.

    Topics: Aged; Alkaloids; Amino Acid Chloromethyl Ketones; Aprotinin; Benzophenanthridines; Benzyl Compounds; Caspase 3; Caspases; Cell Division; Cell Transformation, Neoplastic; Colonic Neoplasms; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Dipeptides; DNA; DNA Fragmentation; Down-Regulation; Humans; Hydrocarbons, Fluorinated; Leucine; Leupeptins; Male; Pepstatins; Phenanthridines; Protein Kinase C; Pyridines; Tumor Cells, Cultured

2003