The potentiation of estrogen on insulin-like growth factor I action in MCF-7 human breast cancer cells includes cell cycle components
The potentiation of estrogen on insulin-like growth factor I action in MCF-7 human breast cancer cells includes cell cycle components
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DOI：
10.1074/jbc.m006741200
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发表时间：
2000-11-17
影响因子：
4.8
通讯作者：
LeRoith, D
中科院分区：
文献类型：
--
作者：
Dupont, J;Karas, M;LeRoith, D
为了深入了解IGF-1受体（IGF-1 R）和雌激素受体信号通路之间的相互作用机制，我们使用了MCF-7衍生细胞（SX 13），其IGF-1 R表达降低了50%。NEO细胞（对照MCF-7细胞）的生长受到IGF-1和雌二醇（E2）的刺激，两种促分裂剂的加入导致协同反应。在NEO细胞中，雌激素增强IGF-1 R信号传导，但在SX 13细胞中，这种作用明显减弱。雌激素也能够增强IGF-1对细胞周期蛋白D1和E的表达以及对视网膜母细胞瘤蛋白磷酸化的影响，但在SX 13细胞中没有。IGF-1增加p21蛋白水平和p21启动子的荧光素酶活性，而它只降低p27蛋白水平而不影响p27启动子活性。雌激素不影响p21抑制剂，但降低p27蛋白水平和p27启动子荧光素酶活性。在细胞周期蛋白依赖性激酶抑制剂与CDK 2的结合水平也观察到两种促分裂剂的这些作用，表明IGF-1和E2影响p21和p27的活性。总之，这些数据表明，在MCF-7细胞中，雌激素增强IGF-1对IGF-1 R信号传导以及细胞周期组分的影响。此外，IGF-I和E2调节p21和p27的表达及其与CDK 2的关联不同。
To gain insight into the mechanisms involved in the cross-talk between IGF-1 receptor (IGF-1R) and estrogen receptor signaling pathways, we used MCF-7-derived cells (SX13), which exhibit a 50% reduction in IGF-1R expression. Growth of NEO cells (control MCF-7 cells) was stimulated by both IGF-1 and estradiol (E2), and the addition of both mitogens resulted in a synergistic response. Estrogen enhanced IGF-1R signaling in NEO cells, but this effect was markedly diminished in SX13 cells. Estrogen was also able to potentiate the IGF-1 effect on the expression of cyclin D1 and cyclin E and on the phosphorylation of retinoblastoma protein in control but not in SX13 cells. IGF-1 increased the protein level of p21 and the luciferase activity of the p21 promoter, whereas it only reduced the protein level of p27 without affecting p27 promoter activity. Estrogen did not affect the p21 inhibitor, but it decreased the protein level of p27 and the p27 promoter luciferase activity. These effects of both mitogens were also observed at the level of association of both cyclin-dependent kinase inhibitors with CDK2 suggesting that IGF-1 and E2 affect the activity of both p21 and p27. Taken together, these data suggest that in MCF-7 cells, estrogen potentiates the IGF-1 effect on IGF-1R signaling as well as on the cell cycle components. Moreover, IGF-I and E2 regulate the expression of p21 and p27 and their association with CDK2 differently.