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 inhibiting 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 associated with MCF-7 cell proliferation. FGF-2 was further used in combination with insulin or cAMP. In MCF-7 cells, insulin and cAMP reversed the mitogenic effect of FGF-2. In MCF-7ras cells, insulin did not modify the inhibitory effect of FGF-2, but cAMP markedly enhanced it. These effects were also associated with an increased level and duration of MAPK activation. PD98056 abolished the effect of FGF-2 on DNA synthesis in both cell lines, demonstrating that the dual effect of FGF-2 on cell proliferation is dependent on the activity of the extracellular-signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway.
Liu
J F
JF
Laboratoire de Recherche Oncologie Moléculaire Humaine, UFR Léonard de Vinci, Université Paris-nord, Bobigny, France.
Issad
T
T
Chevet
E
E
Ledoux
D
D
Courty
J
J
Caruelle
J P
JP
Barritault
D
D
Crépin
M
M
Bertin
B
B
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007328:Insulin; D016222:Fibroblast Growth Factor 2; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases