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:4.1.99.3 (
PRE
)
1,923
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Proteases like
urokinase-type plasminogen activator
(
uPA
) play an important role in tumor invasion. Cells derived from ultraviolet radiation (UVR)-induced corneal sarcomas of Monodelphis domestica produce relatively high levels of
uPA
compared to the untransformed keratocytes suggesting a mechanism for their invasiveness. Because UVR is known to stimulate
uPA
production in many cell types, UVR exposure may further increase
uPA
expression in corneal tumor cells, thus enhancing their ability to infiltrate. We investigated control of basal
uPA
levels and the induction of
uPA
by UVR in transformed and untransformed corneal keratocytes from Monodelphis. These studies took advantage of the fact that Monodelphis possesses an active
photolyase
that can be stimulated to remove UVR-induced pyrimidine dimers by exposure to long-wavelength visible photoreactivating light (PRL). Our studies showed that significant induction of
uPA
occurred in response to 200 J/m2 UVR. This induction was partially blocked by treatment with PRL, indicating that DNA damage, the pyrimidine dimer in particular, played a role in
uPA
induction. In untransformed cultured corneal fibroblasts, the heparin-binding protein inhibitor, suramin, reduced basal
uPA
levels, UVR-induced
uPA
production and cell proliferation. Basic fibroblast growth factor, a heparin-binding growth factor known to be UVR-inducible in mesenchymal cells, stimulated
uPA
production and cell proliferation; however, anti-bFGF antibodies did not significantly decrease proliferation or basal
uPA
production. These findings suggested that basal levels of
uPA
secretion were modulated in response to heparin-binding growth factors and that these growth factors may also have mediated the effect of UVR on
uPA
levels.
...
PMID:Urokinase activity in corneal fibroblasts may be modulated by DNA damage and secreted proteins. 1128 Oct 30
