Insulin-like growth factor-1 promotes cell cycle progression via upregulation of cyclin D1 expression through the phosphatidylinositol 3-kinase/nuclear factor-κB signaling pathway in FRTL thyroid cells
Insulin-like growth factor-1 promotes cell cycle progression via upregulation of cyclin D1 expression through the phosphatidylinositol 3-kinase/nuclear factor-κB signaling pathway in FRTL thyroid cells
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DOI：
10.1038/aps.2008.8
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发表时间：
2009
影响因子：
8.2
通讯作者：
M. Ren;X. Zhong;Chun-yan Ma;Ying Sun;Q. Guan;B. Cui;Jun Guo;Hai Wang;Ling Gao;Jiajun Zha
中科院分区：
文献类型：
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作者：
M. Ren;X. Zhong;Chun-yan Ma;Ying Sun;Q. Guan;B. Cui;Jun Guo;Hai Wang;Ling Gao;Jiajun Zha
目的：胰岛素样生长因子-1（IGF-1）是一种重要的细胞肥大和细胞周期进展因子。已证明IGF-1参与甲状腺增殖和细胞周期进程的调节;然而，这种调节的确切机制尚未完全阐明。在本研究中，我们研究了IGF-1对FRTL甲状腺细胞中细胞周期调控蛋白cyclinD 1表达的影响，以及IGF-1影响cyclinD 1表达的信号通路。根据个体实验的需要，在IGF-1处理前1小时加入磷脂酰肌醇3-激酶（PI 3 K）抑制剂LY 294002和/或核因子-κB（NF-κB）抑制剂BAY 11 -7082。Western blotting检测细胞周期蛋白D1的表达。免疫荧光法检测NF-κB抑制蛋白IκBα的表达。结果：IGF-1可上调甲状腺细胞cyclin D1的表达。用LY 294002或BAY 11 -7082预处理可阻断这种增加。进一步研究表明IGF-1特异性诱导NF-κB活性。结论：IGF-1通过上调细胞周期蛋白D1的表达促进FRTL细胞周期进程，其作用机制可能与PI 3 K/NF-κB信号通路有关。
Aim:Insulin-like growth factor-1 (IGF-1) is an important hypertrophic and cell cycle progression factor for a number of cell types. It has been proven that IGF-1 is involved in the regulation of thyroid proliferation and cell cycle progression; however, the exact mechanism of this regulation has not been fully elucidated. In the present study, we investigated the effect of IGF-1 on the expression of cyclin D1, an important cell cycle regulatory protein, and a signaling pathway involved in IGF-1's effect on cyclinD1 expression in FRTL thyroid cells.Methods:FRTL thyroid cells were treated with IGF-1 or vector control for 24 h. As appropriate to individual experiments, a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and/or a nuclear factor-κB (NF-κB) inhibitor, BAY11-7082, were added 1 h prior to IGF-1 treatment. Western blotting was used to detect cyclin D1 protein expression. Immunofluorescence was performed to analyze the expression of IκBα, an NF-κB inhibitory protein. Cell cycle analysis was performed by fluorescence activated cell sorting (FACS).Results:IGF-1 increased the cyclin D1 expression in thyroid cells. This increase was blocked by pretreatment with LY294002 or BAY11-7082. Further studies showed that IGF-1 specifically induced NF-κB activity. Treatment with IGF-1 could accelerate cell cycle progression from G 0/G 1 to S phase, whereas this progression was inhibited by the presence of LY294002 or BAY11-7082.Conclusion:In summary, the results of the present study show that in FRTL cells, IGF-1 promotes cell cycle progression via an upregulation of cyclin D1 expression, at least partially through the PI3K/NF-κB signaling pathway.