Activation of integrin and ceramide signalling pathways can inhibit the mitogenic effect of insulin-like growth factor I (IGF-I) in human breast cancer cell lines.
Activation of integrin and ceramide signalling pathways can inhibit the mitogenic effect of insulin-like growth factor I (IGF-I) in human breast cancer cell lines.
复制标题
整联蛋白和神经酰胺信号通路的激活可以抑制人类乳腺癌细胞系中胰岛素样生长因子I（IGF-I）的有丝分裂作用。
DOI：
10.1038/sj.bjc.6690113
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发表时间：
1999-02
影响因子：
8.8
通讯作者：
Holly, J M
中科院分区：
文献类型：
--
作者：
Perks, C M;Gill, Z P;Newcomb, P V;Holly, J M
细胞计数，细胞周期分析和Western免疫印迹被用来检查非凋亡剂量的神经酰胺类似物，C2，和合成的精氨酸-甘氨酸-天冬氨酸（RGD）-含有肽，RGD，在MCF-7和T47 D细胞的影响，以确定这些信号通路的激活是否可以改变促有丝分裂的胰岛素样生长因子I（IGF-I）的潜力。IGF-I单独增加两种细胞系中的总细胞数，与细胞周期S期细胞百分比的增加和细胞周期蛋白A产量的同时增加相关。相对于对照组，单独处理对细胞数量或细胞周期蛋白A的产生没有影响。C2抑制IGF-I诱导的有丝分裂在这两个线，而RGD仅在T47 D线有效。尽管抑制细胞增殖，IGF-I刺激的细胞在S期和细胞周期蛋白A的水平不受影响，但是，IGF-I诱导的细胞周期蛋白B1水平的增加被抑制了30%。低剂量诱导整联蛋白和神经酰胺信号传导途径导致细胞在S期被阻断，从而抑制与IGF-I诱导的有丝分裂信号相关的事件的正常周期。激活这些途径不仅可以通过诱导细胞凋亡来限制肿瘤生长，还可以直接抑制IGF-I诱导的细胞增殖。© 1999癌症研究运动
Cell counting, cell cycle analysis and Western immunoblotting were used to examine the effects of non-apoptotic doses of a ceramide analogue, C2, and a synthetic arginine–glycine–aspartic acid (RGD)-containing peptide, RGD, in MCF-7 and T47D cells to determine whether activation of these signalling pathways could alter the mitogenic potential of insulin-like growth factor I (IGF-I). IGF-I alone increased total cell number in both cell lines, associated with a rise in the percentage of cells in the S-phase of the cell cycle and a co-incident increase in cyclin A production. Treatments alone had no effects on cell number or cyclin A production relative to controls. C2 inhibited IGF-I-induced mitogenesis in both lines, whereas RGD was only effective in the T47D line. Despite inhibition of cell proliferation, IGF-I stimulation of cells in S-phase and of cyclin A levels were unaffected; however, an IGF-I-induced increase in cyclin B1 levels was inhibited by 30%. Low-dose induction of integrin and ceramide signalling pathways causes cells to be blocked in S-phase, thereby inhibiting the normal cycle of events associated with the IGF-I-induced mitotic signal. Activating these pathways may not only restrict tumour growth by induction of apoptosis but they may also directly inhibit IGF-I-induced cell proliferation. © 1999 Cancer Research Campaign