Interleukin-1 blocks insulin and insulin-like growth factor-stimulated growth in MCF-7 human breast cancer cells by inhibiting receptor tyrosine kinase activity.
Interleukins-1 (IL-1s) are known to inhibit the growth of cultured breast cancer cells. We examined the effects of IL-1 alpha and IL-1 beta on insulin and insulin-like growth factor I (IGF-I) stimulation of cell growth and found that both IL-1s inhibited anchorage-dependent and independent growth of MCF-7 breast cancer cells. In cells incubated with IL-1 beta (100 U/ml), insulin receptor (IR) protein and messenger RNA were increased by 100%, while IGF-I receptor protein and transcript were not significantly changed. These data were confirmed by binding studies. Incubation of MCF-7 cells with IL-1s led, however, to a significant inhibition of IR and IGF-I receptor autophosphorylation (-55%) and phosphotransferase activity (-65%). Also, in 3T3/ HIR rat fibroblasts, transfected with and overexpressing IR, IL-1s decreased insulin-stimulated cell growth in soft agar and IR tyrosine kinase activity. The present findings suggest that IL-1s antagonize the insulin and IGF-I mitogenic effects in MCF-7 cells by blocking the receptor tyrosine kinase activity that is crucial for the mitogenic effect of these factors.
Costantino
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A
Istituto di Medicina Interna e di Malattie Endocrine e Metaboliche, Cattedra di Endocrinologia, University of Catania, Italy.
Vinci
C
C
Mineo
R
R
Frasca
F
F
Pandini
G
G
Milazzo
G
G
Vigneri
R
R
Belfiore
A
A
D016475:3T3 Cells / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D007328:Insulin; D007375:Interleukin-1; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D020794:Receptor Protein-Tyrosine Kinases; D011972:Receptor, Insulin