Rap1-suppressed tumorigenesis is concomitant with the interference in Ras effector signaling

Expression of Rap1 blocks epithelial growth factor-induced extracellular si gnal-regulated kinases (ERKs) activation. However, recent studies demonstra ted that Rap1 mediates ERKs activation induced by nerve growth factor. The anti-oncogenic effect of Rap1 has been reported but its mechanism remains u nclear. To evaluate the correlation between the anti-transforming effect an d the activation of ERKs, we transfected rap1 cDNA into Hep3B cells and sel ected stable transfectants, The Rap1 transfectants completely lost their in trinsic tumorigenicity in Balb/c nude mice, Both insulin and 12-O-tetradeca noyl phorbol-13-acetate (TPA)-stimulated ERK activations were also blocked, Our findings suggest that Rap1-suppressed tumorigenicity is concomitant wi th ERKs inhibition. (C) 2000 Federation of European Biochemical Societies.