H-Ras is a negative regulator of alpha(3)beta(1) integrin expression in ECV304 endothelial cells

We have examined the role of Ras in integrin expression in ECV304 endotheli al cells. Among the integrins examined in stable ECV304 transfectants expre ssing dominant active H-Ras (DAR-ECV), expression of alpha(3)beta(1) integr in showed a prominent reduction in all the DAR-ECV clones when compared to the parental ECV304 cells. This implies that H-Ras negatively regulates the expression of alpha(3)beta(1) integrin in ECV304 cells. When treated with inhibitors of the Ras downstream pathway (LY294002, PD98059, SB203580), the expression of alpha(3)beta(1) integrin was up-regulated most significantly by LY294002, suggesting that among the downstream pathways of Ras, phospha tidylinositol 3-kinase is a major determinant. With the application of bloc king antibody to alpha(3)beta(1) integrin (2 - 2 x 10(4) nM), migration of ECV304 cells was enhanced to maximal (18%) at 20 nM. These results suggest that migration of endothelial cells could be modulated by H-Ras via alterat ion of the expression levels of alpha(3)beta(1) integrin. (C) 1999 Academic Press.