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 ruffling. We have stably overexpressed rac-1 in JB6 P⁺ cells. In contrast to rac-1 expressing NIH/3T3 cells, all JB6 transfectants expressing rac-1 did not show tumorigenic transformation (forward progression) but instead showed anti- oncogenic effects (backward progression). Transfectants expressing high levels of rac-1 were blocked for TPA-, EGF- and serum-induced transformation, while transfectants expressing lower levels of rac-1 were completely blocked for EGF- and serum-induced transformation but only partially inhibited for TPA-induced transformation compared with vector control transfectants.