Abstract

Transforming growth factor-?1 (TGF-?1) stimulates migration/invasion of mouse transformed keratinocytes and increases urokinase (u-PA) expression/secretion. In this report, we analyzed the biological behavior of two naturally occurring inhibitors of protein tyrosine kinases, genistein and curcumin, that could abrogate the enhancement of u-PA levels induced by TGF-?1 in transformed keratinocytes. Our results showed that genistein and curcumin blocked this response in a dose-dependent manner and also inhibited the TGF-?1-induced synthesis of fibronectin, an early responsive gene to the growth factor. Both compounds also reduced TGF-?1-stimulated cell migration and invasiveness. These results suggest that a tyrosine kinase-signaling pathway should be involved in TGF-?1-mediated increased malignancy of transformed keratinocytes and that genistein and curcumin could play an important role in inhibiting tumor progression.