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首页> 外文期刊>Oncogene >Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3B
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Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3B

机译：鉴定IGFBP-6作为SEMA3B的抑癌活性的效应子

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SEMA3B, a member of class 3 semaphorins, is a tumor suppressor. Competition with vascular endothelial growth factor (VEGF)165 explains a portion of the activity, whereas the VEGF-independent mechanism was not elucidated. We employed a microarray and screened for the genes whose expression was increased by SEMA3B in NCI-H1299 cells. Insulin-like growth factor-binding protein-6 (IGFBP-6), a tumor suppressor, showed greatest difference in the expression level. Introduction of IGFBP-6 cDNA reduced colony formation both on the dish surface and in soft agar. Insulin-like growth factor II, which antagonizes IGFBP-6, partly abrogated the effect. Inhibition of IGFBP-6 by small interfering RNA diminished the sub-G0/G1 population that was induced by SEMA3B and abrogated the growth suppressive effect of SEMA3B. We concluded that IGFBP-6 is the effector of tumor suppressor activity of SEMA3B in NCI-H1299 cells. It has been reported that β-catenin suppresses the expression of IGFBP-6. Introduction of β-catenin into the cells partly abrogated the growth suppressive effect of SEMA3B. Our result indicates that semaphorin signaling and β-catenin signaling converge on IGFBP-6 and antithetically affect their functions.
机译：SEMA3B是3类信号量的成员，是一种肿瘤抑制因子。与血管内皮生长因子（VEGF）165的竞争解释了部分活性，而未阐明VEGF非依赖性机制。我们采用了微阵列，并筛选了SEMA3B在NCI-H1299细胞中表达增加的基因。胰岛素样生长因子结合蛋白6（IGFBP-6）是一种肿瘤抑制因子，其表达水平差异最大。引入IGFBP-6 cDNA可减少培养皿表面和软琼脂中的菌落形成。拮抗IGFBP-6的胰岛素样生长因子II部分废除了该作用。小干扰RNA抑制IGFBP-6减少了SEMA3B诱导的sub-G0 / G1种群，并废除了SEMA3B的生长抑制作用。我们得出结论，IGFBP-6是NCI-H1299细胞中SEMA3B的抑癌活性的效应子。据报道，β-连环蛋白抑制IGFBP-6的表达。将β-连环蛋白引入细胞部分消除了SEMA3B的生长抑制作用。我们的结果表明，信号蛋白和β-catenin信号在IGFBP-6上会聚，并从理论上影响其功能。

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