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Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA synthesis in MCF-7 cells
- Source :
- Oncogene. 18(47)
- Publication Year :
- 1999
-
Abstract
- 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.
- Subjects :
- DNA Replication
rac1 GTP-Binding Protein
Cancer Research
medicine.medical_specialty
Biology
Fibroblast growth factor
medicine.disease_cause
chemistry.chemical_compound
Internal medicine
Genetics
medicine
Tumor Cells, Cultured
Humans
Tyrosine
Phosphorylation
Molecular Biology
Adaptor Proteins, Signal Transducing
DNA Primers
Oncogene Proteins
DNA synthesis
Base Sequence
Membrane Proteins
Tyrosine phosphorylation
Phosphoproteins
Cell biology
Proto-Oncogene Proteins c-raf
Endocrinology
chemistry
Cell culture
Fibroblast Growth Factor 2
Signal transduction
Mitogen-Activated Protein Kinases
Carcinogenesis
Signal Transduction
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 18
- Issue :
- 47
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....c6f37f63fac8bb2e822920899ca00607