INHIBITION OF TUMOR PROMOTER INDUCED TRANSFORMATION BY EXPRESSION OF THE SMALL GTP-BINDING PROTEIN RAC IN JB6 CELLS

The small GTP-binding protein rac-1 has been reported to be a mediator for tumor promoter, growth factor and serum-induced cell membrane ruf fling. We have stably overexpressed rac-1 in JB6 P+ cells. In contrast to rac-1 expressing NIH/3T3 cells, all JB6 transfectants expressing r ac-1 did not show tumorigenic transformation (forward progression) but instead showed anti-oncogenic effects (backward progression). Transfe ctants expressing high levels of rac-1 were blocked for TPA-, EGF- and serum-induced transformation, while transfectants expressing lower le vels of rac-1 were completely blocked for EGF- and serum-induced trans formation but only partially inhibited for TPA-induced transformation compared with vector control transfectants.