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Modulation by interleukin-2 of cellular response to fibroblast growth factor-1 in F69-3 fibrosarcoma cells
P Zalecki1, C Radzikowski, S Olsnes
1Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
Abstract:
FGF-1 stimulated DNA synthesis and induced expression of IL-2 receptors in the murine fibrosarcoma cell line, F69-3. Concomitant treatment with IL-2 abolished the stimulation of DNA synthesis, but not binding of FGF-1 to the FGF-receptors or subsequent endocytosis of the bound growth factor. Also, it did not inhibit activation of the FGF-receptor tyrosine kinase or stimulation of the downstream effector, MAP kinase. Treatment with IL-2 prevented transport of FGF-1 to the nuclear fraction in a time- and dose-dependent manner that parallelled the inhibition of FGF-1 stimulated DNA synthesis. The data support our earlier finding that transport of FGF-1 to the nucleus is an important event in the mechanism of stimulation of DNA synthesis induced by the growth factor, and they demonstrate that treatment with a cytokine can modulate the cellular response to FGF-1.
Insights
Interleukin-2 (IL-2) inhibits fibroblast growth factor-1 (FGF-1) stimulated DNA synthesis by preventing nuclear transport of FGF-1 in fibrosarcoma cells. This cytokine modulation highlights a key regulatory mechanism in cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Fibroblast Growth Factor-1 (FGF-1) is a potent stimulator of DNA synthesis.
- Interleukin-2 (IL-2) is a cytokine involved in immune responses and cell growth regulation.
- Understanding the interplay between FGF-1 and IL-2 is crucial for cancer research.
Purpose of the Study:
- To investigate the effect of IL-2 on FGF-1-induced DNA synthesis in murine fibrosarcoma cells.
- To elucidate the molecular mechanisms by which IL-2 modulates FGF-1 signaling.
- To determine the role of FGF-1 nuclear transport in growth factor-induced DNA synthesis.
Main Methods:
- Murine fibrosarcoma cell line (F69-3) was used for experiments.
- Cells were treated with FGF-1 and/or IL-2.
- DNA synthesis, IL-2 receptor expression, FGF-1 binding, endocytosis, receptor tyrosine kinase activation, MAP kinase activation, and FGF-1 nuclear transport were assessed.
Main Results:
- FGF-1 stimulated DNA synthesis and IL-2 receptor expression.
- IL-2 abolished FGF-1-stimulated DNA synthesis but did not affect FGF-1 binding, endocytosis, or downstream signaling (tyrosine kinase, MAP kinase).
- IL-2 inhibited FGF-1 transport to the nucleus in a time- and dose-dependent manner.
Conclusions:
- Nuclear transport of FGF-1 is essential for FGF-1-induced DNA synthesis.
- IL-2 modulates cellular responses to FGF-1 by inhibiting FGF-1 nuclear translocation.
- Cytokines can regulate growth factor-mediated cell proliferation, offering potential therapeutic insights.
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