Our previous studies have demonstrated that basic fibroblast growth factor (bFGF) inhibits the growth of MCF-7 human breast cancer cells via binding to high affinity cell surface receptors. The downstream signaling of bFGF was reported to involve the ras pathway. The aim of the present study was to examine the bFGF-induced growth inhibition in the presence of lovastatin, a farnesyl transferase inhibitor, which impaired ras signaling by preventing its association with the plasma membrane. We found that the combined cytotoxicity induced by lovastatin and bFGF was greater than the cytotoxicity induced by each agent alone. Similarly, the protein level of P21/WAF1/cip1 was greater after exposure to both agents together, than separately. bFGF did not interfere with the lovastatin-induced inhibition of P21/RAS membrane association, while lovastatin did not prevent MAPK activation by bFGF. Based on these findings we suggest that the growth inhibitory effect of bFGF on breast cancer cells is largely independent of the ras signaling pathway. Understanding these pathways may enable active intervention to alter the therapeutic ratio favorably in the treatment of breast cancer.

Related Articles