Genistein and curcumin block TGF-beta(1)-induced u-PA expression and migratory and invasive phenotype in mouse epidermal keratinocytes

Transforming growth factor-beta(1) (TGF-beta(1)) stimulates migration/invas ion of mouse transformed keratinocytes and increases urokinase (u-PA) expre ssion/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 -beta(1) in transformed keratinocytes. Our results showed that genistein an d curcumin blocked this response in a dose-dependent manner and also inhibi ted the TGF-beta(1)-induced synthesis of fibronectin, an early responsive g ene to the growth factor. Both compounds also reduced TCF-beta(1)-stimulate d cell migration and invasiveness. These results suggest that a tyrosine ki nase-signaling pathway should be involved in TGF-beta(1)-mediated increased malignancy of transformed keratinocytes and that genistein and curcumin co uld play an important role in inhibiting tumor progression.