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 have previously found that in the human neuroblastoma cell line SY5Y the SST analogue 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-induced Ras activation in a pertussis toxin (PTx)-independent and peroxovanadate-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, likely accounting for the SST-mediated inhibition of PDGF-induced Ras activation.
Cattaneo
M G
MG
Department of Pharmacology, University of Milano, Via Vanvitelli, 32, 20129, Milano, Italy.
Scita
G
G
Vicentini
L M
LM
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D013004:Somatostatin / Q000502:physiology*; D014407:Tumor Cells, Cultured; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; C102193:RASA2 protein, human; D020703:ras GTPase-Activating Proteins; D013004:Somatostatin; D017479:Receptors, Platelet-Derived Growth Factor; D018631:ras Proteins