Boelaert K, Tannahill L A, Bulmer J N, Kachilele S, Chan S Y, Kim D, Gittoes N J L, Franklyn J A, Kilby M D, McCabe C J
Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
FASEB J. 2003 Sep;17(12):1631-9. doi: 10.1096/fj.02-0948com.
Human securin, known also as PTTG, has established oncogenic and cell cycle regulatory functions. PTTG/securin transforms cells in vitro, inhibits sister chromatid separation, and regulates secretion of fibroblast growth factor-2. FGF-2 is a key regulator of CNS development and PTTG/securin expression has been reported in murine fetal brain. We examined the expression and function of securin and FGF-2 in the developing human fetal brain and in a fetal neuronal cell line (NT 2). Securin expression was significantly reduced in first and second trimester fetal cerebral cortex compared with adult cerebral cortex, where immunocytochemistry revealed intense securin staining in neuronal cell bodies. FGF-2 protein was concordantly lower in fetal cortex, whereas pretranslational expression of PTTG binding factor (PBF) was not significantly altered in fetal brain compared with adult. PCNA expression demonstrated that high securin levels in adult cortex were associated with absent cell proliferation. In NT-2 cells, securin stimulated FGF-2 expression, which could be abrogated by a carboxyl-terminal mutation. Low transient expression of securin resulted in a significant proliferative effect, whereas high levels of securin expression inhibited cell turnover. We propose a potential role for human PTTG/securin in modulating cell proliferation and FGF-2 expression during human neurogenesis.
人分裂周期蛋白，也称为垂体肿瘤转化基因（PTTG），已被证实具有致癌和细胞周期调节功能。PTTG/分裂周期蛋白在体外可使细胞发生转化，抑制姐妹染色单体分离，并调节成纤维细胞生长因子-2（FGF-2）的分泌。FGF-2是中枢神经系统发育的关键调节因子，并且在小鼠胎脑中已报道有PTTG/分裂周期蛋白的表达。我们检测了分裂周期蛋白和FGF-2在发育中的人类胎儿大脑以及一种胎儿神经元细胞系（NT 2）中的表达和功能。与成人脑皮质相比，在妊娠早期和中期胎儿的大脑皮质中，分裂周期蛋白的表达显著降低，免疫细胞化学显示在神经元细胞体中有强烈的分裂周期蛋白染色。胎儿皮质中FGF-2蛋白的含量相应较低，而与成人相比，胎儿脑中PTTG结合因子（PBF）的翻译前表达没有显著改变。增殖细胞核抗原（PCNA）的表达表明，成人皮质中高水平的分裂周期蛋白与细胞增殖的缺乏有关。在NT-2细胞中，分裂周期蛋白刺激FGF-2的表达，而这种刺激可被羧基末端突变消除。分裂周期蛋白的低瞬时表达导致显著的增殖效应，而高水平表达则抑制细胞更新。我们提出人PTTG/分裂周期蛋白在人类神经发生过程中调节细胞增殖和FGF-2表达方面可能发挥作用。
