Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Urokinase plasminogen activator
(
uPA
) is a multifunctional protein involved in both extracellular proteolysis and signal transduction.
uPA
usually mediates its actions while attached to a membrane-bound receptor, termed uPAR. In this study,
uPA
and its receptor were measured at both protein and mRNA levels in breast cancer. At both levels, concentrations of
uPA
were significantly correlated with those for uPAR.
uPA
levels also correlated significantly with cathepsin B and cathepsin D but not with cathepsin L,
MMP-8
or MMP-9 levels. Irrespective of the cut-off point used (e.g., median, tertile or quartile values),
uPA
was a significant prognostic marker for breast cancer.
...
PMID:Urokinase plasminogen activator as a predictor of aggressive disease in breast cancer. 879 99
Urokinase plasminogen activator
(
uPA
) has been associated with invasion and metastasis in breast cancer. The expression of
uPA
and 92 kDa type IV collagenase (gelatinase B/MMP-9) is regulated by growth factors, receptor-type tyrosine kinases and cytoplasmic oncoproteins. Here, we have identified transcriptional requirements for the induction of
uPA
and 92 kDa type IV collagenase by epidermal growth factor (EGF). EGF stimulates the motile and invasive activities specifically in the ErbB-2-overexpressing SK-BR-3 cells. Expression of extracellular matrix-degrading proteases including type I collagenase/
MMP-1
, 92 kDa type IV collagenase/MMP-9,
uPA
and
uPA
receptor were induced. EGF also transiently stimulated expression of the transcription factors Ets-1 and Ets-2. Reporter transfection assays revealed the activation of
uPA
and MMP-9
collagenase
promoters by EGF and the requirement of each of the composite Ets and AP-1 transcription factor binding sites for an EGF response. Most notably, transfections with the Ets-1 and Ets-2 expression vectors potentiated
uPA
and MMP-9 promoter activation in response to EGF. Mutation of the threonine 75 residue of chicken Ets-2 conserved in the Pointed group of the Ets family proteins abrogated the ability of Ets-2 to collaborate with EGF. Ets-1 and Ets-2 were highly expressed in invasive breast tumor cell lines. Our results suggest that Ets-1 and Ets-2 provide the link connecting EGF stimuli with activation of
uPA
and 92 kDa type IV collagenase promoters and may contribute to invasion phenotypes.
...
PMID:The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor. 963 4
