Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice

Whereas the GTPase RhoA has been shown to promote proliferation and maligna nt transformation, the involvement of RhoB in these processes is not well u nderstood. In this manuscript RhoB is shown to be a potent suppressor of tr ansformation and human tumor growth in nude mice. In several human cancer c ell lines, RhoA promotes focus formation whereas RhoB is as potent as the t umor suppressor p53 at inhibiting transformation in this assay. RhoB is bot h farnesylated (F) and geranylgeranylated (GG), and RhoB-F has been suggest ed as a target for the antitumor activity of farnesyltransferase inhibitors . Here we demonstrate that both RhoB-F and RhoB-GG inhibit anchorage-depend ent and -independent growth, induce apoptosis, inhibit constitutive activat ion of Erk and insulin-like growth factor-1 stimulation of Akt, and suppres s tumor growth in nude mice. The data demonstrate that RhoB is a potent sup pressor of human tumor growth and that RhoB-F is not a target for farnesylt ransferase inhibitors.