PMID- 10965519 OWN - NLM STAT- MEDLINE DCOM- 20010531 LR - 20181130 IS - 0163-5581 (Print) IS - 0163-5581 (Linking) VI - 37 IP - 1 DP - 2000 TI - Genistein and curcumin block TGF-beta 1-induced u-PA expression and migratory and invasive phenotype in mouse epidermal keratinocytes. PG - 49-54 AB - Transforming growth factor-beta 1 (TGF-beta 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-beta 1 in transformed keratinocytes. Our results showed that genistein and curcumin blocked this response in a dose-dependent manner and also inhibited the TGF-beta 1-induced synthesis of fibronectin, an early responsive gene to the growth factor. Both compounds also reduced TGF-beta 1-stimulated cell migration and invasiveness. These results suggest that a tyrosine kinase-signaling pathway should be involved in TGF-beta 1-mediated increased malignancy of transformed keratinocytes and that genistein and curcumin could play an important role in inhibiting tumor progression. FAU - Santibanez, J F AU - Santibanez JF AD - Laboratorio de Biologia Celular, INTA, Universidad de Chile, Santiago, Chile. FAU - Quintanilla, M AU - Quintanilla M FAU - Martinez, J AU - Martinez J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Nutr Cancer JT - Nutrition and cancer JID - 7905040 RN - 0 (Transforming Growth Factor beta) RN - DH2M523P0H (Genistein) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Blotting, Western MH - Cell Movement/drug effects MH - Cells, Cultured MH - Curcumin/*pharmacology MH - Epidermal Cells MH - Epidermis/drug effects MH - Fluorescent Antibody Technique MH - Genistein/antagonists & inhibitors/*pharmacology MH - Keratinocytes/cytology/*drug effects/metabolism MH - Mice MH - Protein-Tyrosine Kinases/metabolism MH - Transforming Growth Factor beta/*pharmacology MH - Urokinase-Type Plasminogen Activator/*drug effects/metabolism EDAT- 2000/08/31 11:00 MHDA- 2001/06/02 10:01 CRDT- 2000/08/31 11:00 PHST- 2000/08/31 11:00 [pubmed] PHST- 2001/06/02 10:01 [medline] PHST- 2000/08/31 11:00 [entrez] AID - 10.1207/S15327914NC3701_6 [doi] PST - ppublish SO - Nutr Cancer. 2000;37(1):49-54. doi: 10.1207/S15327914NC3701_6.