FIBROBLAST GROWTH FACTOR-2 HAS OPPOSITE EFFECTS ON HUMAN BREAST-CANCER MCF-7 CELL-GROWTH DEPENDING ON THE ACTIVATION LEVEL OF THE MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY

In human breast cancer MCF-7 and MCF-7ras cells, we demonstrated that whereas insulin had a mitogenic effect on both cell lines, fibroblast growth factor-2 (FGF-2) had opposite effects, stimulating MCF-7 and in hibiting MCF-7ras cell proliferation. The inhibitory signal induced by FGF-2 was related to sustained mitogen-activated protein kinase (MAPK ) activation in MCF-7ras cells, while transient MAPK activation was as sociated with MCF-7 cell proliferation. FGF-2 was further used in comb ination with insulin or cAMP. In MCF-7 cells, insulin and cAMP reverse d the mitogenic effect of FGF-2. In MCF-7ras cells, insulin did not mo dify the inhibitory effect of FGF-2, but cAMP markedly enhanced it. Th ese effects were also associated with an increased level and duration of MAPK activation. PD98056 abolished the effect of FGF-2 on DNA synth esis in both cell lines, demonstrating that the dual effect of FGF-2 o n cell proliferation is dependent on the activity of the extracellular -signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway.