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Secretion of urokinase and metalloproteinase‐9 induced by staurosporine is dependent on a tyrosine kinase pathway in mammary tumor cells
Author(s) -
Aguirre Ghiso Julio A.,
Farías Eduardo F.,
Alonso Daniel F.,
Bal De Kier Joffé Elisa
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980504)76:3<362::aid-ijc13>3.0.co;2-d
Subject(s) - staurosporine , protein kinase c , secretion , biology , protein kinase a , tyrosine kinase , kinase , microbiology and biotechnology , signal transduction , endocrinology
Urokinase‐type plasminogen activator (uPA) is a key serine protease involved in invasion and metastasis. We had shown that overproduction of uPA in tumor cells is controlled by a phospholipase D‐protein kinase C‐dependent pathway. Now we studied whether other signaling pathways participate in the regulation of constitutive uPA and metalloproteinase (MMP) overproduction in tumor cells. Staurosporine, a protein kinase inhibitor, stimulated uPA and MMP‐9 secretion as measured by radial caseinolysis, zymography and Western blotting. Genistein, a specific tyrosine kinase inhibitor, reduced the constitutive and staurosporine‐induced uPA and MMP‐9 secretion. Interestingly, the phosphatase inhibitor vanadate stimulated uPA secretion. Verapamil, a calcium channel blocker, inhibited both endogenous and PMA‐stimulated secretion of uPA but was unable to inhibit staurosporine‐induced secretion. The alcohol n‐butanol, a phospholipase D and protein kinase C inhibitor, besides inhibiting constitutive uPA secretion, blocked staurosporine‐induced secretion. Our results suggest that constitutive and staurosporine‐induced uPA and MMP‐9 secretion by LM3 murine mammary tumor cells is controlled by an endogenous tyrosine kinase pathway and probably involves protein phosphatases. In addition, the staurosporine‐induced signal regulating urokinase secretion is independent of extracellular calcium but dependent on phospholipase D. Int. J. Cancer 76:362–367, 1998.© 1998 Wiley‐Liss, Inc.