Functional Rac-1 and Nck signaling networks are required for FGF-2-inducedDNA synthesis in MCF-7 cells

The effects of Fibroblast Growth Factor-2 (FGF-2) on breast cancer cell DNA synthesis are controversial. To elucidate the mechanisms by which FGF-2 st imulates or inhibits DNA synthesis, we analysed FGF-2 signaling pathways in breast cancer MCF-7 and MCF-7 cells overexpressing Ha-Ras (MCF-7ras), We f ound that FGF-2-induction of DNA synthesis correlates with Ras transient ac tivation, FRS-2 tyrosine phosphorylation and low level of expression of p66 (She). In addition, Nck-associated proteins are highly tyrosine phosphoryla ted and JNK reaches a higher level of activation when FGF-2 triggers DNA sy nthesis. Interestingly upon FGF-2 treatment, JNK activation and DNA synthes is are dependent on Rac-1 activity. These results confirm that in MCF-7 cel ls, induction of DNA synthesis by FGF-2 requires a transient activation of the Ras/MAPK cascade and demonstrates for the first time that intact Rac-1 and Nck signaling networks are required.