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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion
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IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion

机译:IIp45是一种胰岛素样生长因子结合蛋白2(IGFBP-2)结合蛋白,可拮抗IGFBP-2刺激神经胶质瘤细胞侵袭

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Our previous studies have shown that insulin-like growth factor binding protein 2 (IGFBP-2) is frequently overexpressed in the highly invasive glioblastoma multiforme (GBM). By using a yeast two-hybrid system, we identified a gene, invasion inhibitory protein 45 (IIp45), whose protein product bound to IGFBP-2 through the thyroglobulin-RGD region of the C terminus of IGFBP-2. The IIp45 gene is located on chromosome 1p36 and has nine exons. The IIp45 protein has three SEG (segment of low compositional complexity) domains and an integrin-binding RGD motif. The IIp45 protein was not expressed in some GBMs. Functional studies showed that IIp45 inhibited GBM cell invasion both in vitro and in xenograft model. Gene expression profiling studies showed that IIp45 consistently inhibited the expression of cell invasion-associated genes, such as the transcriptional NFκB, and its downstream target gene, intercellular adhesion molecule 1. Thus, we report here the isolation and characterization of a gene, IIp45, whose protein product binds to IGFBP-2 and inhibits glioma cell invasion.
机译:我们以前的研究表明,胰岛素样生长因子结合蛋白2(IGFBP-2)在高侵袭性胶质母细胞瘤(GBM)中经常过表达。通过使用酵母双杂交系统,我们确定了一个基因,入侵抑制蛋白45(IIp45),其蛋白产物通过IGFBP-2 C端的甲状腺球蛋白-RGD区与IGFBP-2结合。 IIp45基因位于染色体1p36上,具有9个外显子。 IIp45蛋白具有三个SEG(低组成复杂度的片段)结构域和一个整合素结合的RGD基序。 IIp45蛋白在某些GBM中未表达。功能研究表明,IIp45在体外和异种移植模型中均能抑制GBM细胞侵袭。基因表达谱研究表明,IIp45始终抑制与细胞侵袭相关的基因(例如转录NFκB)及其下游靶基因即细胞间粘附分子1的表达。因此,在此我们报道了IIp45基因的分离和鉴定,其蛋白产物与IGFBP-2结合并抑制神经胶质瘤细胞侵袭。

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