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c‐jun‐NH2JNK mediates invasive potential and EGFR activation by regulating the expression of HB‐EGF in a urokinase‐stimulated pathway
Author(s) -
Cáceres Mónica,
Tobar Nicolás,
Guerrero Javier,
Smith Patricio C.,
Martínez Jorge
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21469
Subject(s) - autocrine signalling , phosphorylation , epidermal growth factor , microbiology and biotechnology , tyrosine kinase , chemistry , kinase , tyrosine phosphorylation , cancer research , signal transduction , biology , receptor , biochemistry
In this study, we demonstrated that tyrosine phosphorylation of EGFR and the autocrine expression of uPA and HB‐EGF depend on the activity of c‐jun amino‐terminal kinase (JNK) in human prostatic DU‐145 cells. These cells overexpress EGFR and produce a high amount of uPA. Treatment with either SP600125, a specific chemical inhibitor of JNK, or the expression of a dominant‐negative JNK form inhibited autocrine production of uPA and HB‐EGF, which block EGFR phosphorylation and mitigates invasive capacity. Our data provided evidence that in DU‐145 cells, the maintenance of the activation level of EGFR, which determines the cellular invasive potential, operates through an autocrine loop involving the JNK‐dependent production of uPA and HB‐EGF activity. Moreover, we found that exogenously added uPA stimulates autocrine production of HB‐EGF, and that blocking HB‐EGF activity curbed DU‐145 cell invasive potential. J. Cell. Biochem. 103: 986–993, 2008. © 2007 Wiley‐Liss, Inc.