Interleukin-1 blocks insulin and insulin-like growth factor-stimulated growth in MCF-7 human breast cancer cells by inhibiting receptor tyrosine kinase activity

• Published in: Endocrinology (Philadelphia) 1996-10, Vol.137 (10), p.4100-4107
• Main Authors: Costantino, A, Vinci, C, Mineo, R, Frasca, F, Pandini, G, Milazzo, G, Vigneri, R, Belfiore, A
• Format: Article
• Language: English
• Subjects: 3T3 Cells - metabolism; Animals; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Division - drug effects; Cell growth; Growth factors; Humans; Insulin; Insulin - pharmacology; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factors; Interleukin 1; Interleukin-1 - pharmacology; Interleukins; Kinases; Mice; mRNA; Phosphotransferase; Protein-tyrosine kinase receptors; Proteins; Rats; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Receptor, Insulin - drug effects; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Receptors; Receptors, Somatomedin - drug effects; Receptors, Somatomedin - genetics; Receptors, Somatomedin - metabolism; Recombinant Proteins; RNA, Messenger - metabolism; Tumor Cells, Cultured; Tyrosine
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.137.10.8828463

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.