Costantino A, Vinci C, Mineo R, Frasca F, Pandini G, Milazzo G, Vigneri R, Belfiore A
Istituto di Medicina Interna e di Malattie Endocrine e Metaboliche, Cattedra di Endocrinologia, University of Catania, Italy.
Endocrinology. 1996 Oct;137(10):4100-7. 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.
白细胞介素 -1（IL -1s）已知可抑制培养的乳腺癌细胞生长。我们研究了IL -1α和IL -1β对胰岛素及胰岛素样生长因子I（IGF -I）刺激细胞生长的影响，发现这两种IL -1s均抑制MCF -7乳腺癌细胞的贴壁依赖性和非贴壁依赖性生长。在用IL -1β（100 U/ml）孵育的细胞中，胰岛素受体（IR）蛋白和信使核糖核酸增加了100%，而IGF -I受体蛋白和转录本没有显著变化。这些数据通过结合研究得到证实。然而，用IL -1s孵育MCF -7细胞导致IR和IGF -I受体自身磷酸化显著抑制（-55%）以及磷酸转移酶活性显著抑制（-65%）。同样，在转染并过表达IR的3T3/HIR大鼠成纤维细胞中，IL -1s降低了软琼脂中胰岛素刺激的细胞生长以及IR酪氨酸激酶活性。目前的研究结果表明，IL -1s通过阻断对这些因子促有丝分裂作用至关重要的受体酪氨酸激酶活性，拮抗MCF -7细胞中胰岛素和IGF -I的促有丝分裂作用。
