H. Kobayashi et al., Suppression of urokinase-type plasminogen activator expression from human ovarian cancer cells by urinary trypsin inhibitor, BBA-PROT ST, 1481(2), 2000, pp. 310-316
Citations number
23
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY
Urinary trypsin inhibitor (UTI), a Kunitz-type protease inhibitor, efficien
tly inhibits tumor cell invasion and metastasis. We examined the effect of
UTI on urokinase-type plasminogen activator (uPA) expression in ovarian can
cer cell lines, HOC-I and HRA. By Northern blot, Western blot, ELISA, and z
ymographic analyses, we demonstrated that UTI inhibited the expression of u
PA mRNA and protein in these cells in a time- and dose-dependent manner, in
dependent of whether induction was triggered by phorbol ester. Monoclonal a
ntibody 4G12, which inhibits Un binding to the cells, produced a dose-depen
dent abrogation in UTI-mediated down-regulation of uPA expression. These da
ta suggest that UTI significantly down-regulates tumor cell uPA mRNA expres
sion and protein secretion, and that UTI binding to the cells is necessary
to exert the UTI's action. (C) 2000 Elsevier Science B.V. All rights reserv
ed.