Modulation by interleukin-2 of cellular response to fibroblast growth factor-1 in F69-3 fibrosarcoma cells.
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.
Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
P
P
Zalecki
C
C
Radzikowski
S
S
Olsnes
A
A
Wiedłocha
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011485:Protein Binding / Q000187:drug effects; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007376:Interleukin-2; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases