Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA 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 stimulates 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 found that FGF-2-induction of DNA synthesis correlates with Ras transient activation, FRS-2 tyrosine phosphorylation and low level of expression of p66Shc. In addition, Nck-associated proteins are highly tyrosine phosphorylated and JNK reaches a higher level of activation when FGF-2 triggers DNA synthesis. Interestingly upon FGF-2 treatment, JNK activation and DNA synthesis are dependent on Rac-1 activity. These results confirm that in MCF-7 cells, 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.
Liu
J F
JF
Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.
Chevet
E
E
Kebache
S
S
Lemaitre
G
G
Barritault
D
D
Larose
L
L
Crépin
M
M
D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D017931:DNA Primers; D004261:DNA Replication / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C106534:FRS2 protein, human; D008565:Membrane Proteins; C078332:Nck protein; D015513:Oncogene Proteins; D010750:Phosphoproteins; D016222:Fibroblast Growth Factor 2; D014443:Tyrosine; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein