c-jun-NH2JNK mediates invasive potential and EGFR activation by regulating the expression of HB-EGF in a urokinase-stimulated pathway

Cáceres M.; Tobar, N.; Guerrero, J; Smith, PC; Martinez, J.

Abstract

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. © 2007 Wiley-Liss, Inc.

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Título según WOS: c-jun-NH2JNK mediates invasive potential and EGFR activation by regulating the expression of HB-EGF in a urokinase-stimulated pathway
Título según SCOPUS: c-jun-NH2JNK mediates invasive potential and EGFR activation by regulating the expression of HB-EGF in a urokinase-stimulated pathway
Título de la Revista: JOURNAL OF CELLULAR BIOCHEMISTRY
Volumen: 103
Número: 3
Editorial: WILEY-BLACKWELL
Fecha de publicación: 2008
Página de inicio: 986
Página final: 993
Idioma: English
URL: http://doi.wiley.com/10.1002/jcb.21469
DOI:

10.1002/jcb.21469

Notas: ISI, SCOPUS