Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
Disease
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Query: EC:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The signal transduction cascade initiated by the activation of phosphoinositide 3-kinase (PI-3 kinase) is implicated in mitogenic and antiapoptotic signaling generated by growth factors in a variety of cell types. We have examined the consequences of an inhibition of this pathway in human diploid fibroblasts. We find that a specific PI-3 kinase inhibitor (LY294002) causes growth arrest in these cells accompanied by changes in gene expression that are similar to those seen during cellular senescence. A second inhibitor, PD58029, which is specific for the
mitogen-activated protein kinase kinase 1
(MEK-1), also induces a growth arrest but does not induce the same spectrum of gene expression. The pattern of gene expression in the presence the MEK-1 inhibitor is similar to that seen during growth arrest induced by serum starvation. The specific phenotypic changes seen following inhibition of PI-3 kinase are: an increase in beta-galactosidase activity; a decrease in EPC-1 gene expression; and a dramatic increase in
collagenase
gene expression. Thus, growth arrest with a PI-3 kinase inhibitor induces a senescent-like phenotype that is not seen when cells are growth arrested by either serum starvation or a MEK-1 inhibitor.
...
PMID:A phosphatidylinositol 3-kinase inhibitor induces a senescent-like growth arrest in human diploid fibroblasts. 981 8
The aim of the current study was to confirm that tenascin-C large splice variant (TNC320) stimulates
matrix metalloproteinase-1
(
MMP-1
) expression and to elucidate molecular mechanisms underlying this activation. The analysis of gene expression in cultured cells grown under different conditions indicated significant increases of
MMP-1
mRNA steady-state levels in the cells treated with TNC320 (200%) compared with TNC220 (100%) and bovine serum albumin (BSA), which served as controls. Gel electrophoresis results demonstrated augmented
MMP-1
protein in cells cultured with TNC320, whereas slight up-regulation was noticed in cells treated with TNC220 or fibronectin. Reverse transcriptase polymerase chain reaction results demonstrated significantly higher levels of
MMP-1
gene expression in TNC320 cultured cells than in all other treatment groups. The result was confirmed by examining the level of
MMP-1
promoter transactivation by different extracellular proteins. Data demonstrated 30-fold activation of
MMP-1
promoter by TNC320 treatment in comparison with other treatments (TNC220 or fibronectin) and BSA as a control. Both invasion and
collagenase
activity assays demonstrated a 3-fold difference in the cells treated with TNC320 in comparison with the control.
MMP-1
was quantified by enzyme-linked immunosorbent assay as well. Experiments with constitutively active expression kinases indicated that
MMP-1
expression induced by TNC320 was associated with mitogen-activated protein kinase (MAPK) cascade activation. Culture with TNC320 resulted in more than 2-fold activation of MMP1-luciferase in the presence of mitogen-activated protein kinase kinase kinase 1 and also 2-fold down-regulation in the presence of
mitogen-activated protein kinase kinase 1
. We hypothesize that tenascin-C stimulates invasion via up-regulation of
MMP-1
expression through activation of MAPK cascade signaling.
...
PMID:Molecular mechanism of tenascin-C action on matrix metalloproteinase-1 invasive potential. 1739 87
