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.

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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