Somatostatin inhibits PDGF-stimulated Ras activation in human neuroblastoma cells

The main physiological role of somatostatin (SST) is the control of hormone secretion. Recently, SST has been shown to exert antiproliferative effects on some human tumors via both direct and indirect mechanisms. We hale prev iously found that in the human neuroblastoma cell line SY5Y the SST analogu e lanreotide (BIM 23014) inhibited serum-stimulated cell proliferation and MAP kinase activity. Here, we examine the effect of SST on PDGF-induced Ras activation. We found that SST suppressed PDGF-indueed Res activation in a pertussis toxin (PTx)-independent and perosovanadate-dependent manner. Ras- specific GTPase activating protein (GAP) activities,were not altered by SST treatment. On the contrary, PDGF-induced PDGF receptor phosphorylation was decreased by SST in a PTx-independent, peroxovanadate-dependent manner, li kely accounting for the SST-mediated inhibition of PDGF-induced Ras activat ion, (C) 1999 Federation of European Biochemical Societies.