TWIST-1 is overexpressed in neoplastic choroid plexus epithelial cells and promotes proliferation and invasion.
TWIST-1 is overexpressed in neoplastic choroid plexus epithelial cells and promotes proliferation and invasion.
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DOI：
10.1158/0008-5472.can-08-3176
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发表时间：
2009-03-15
期刊：
影响因子：
11.2
通讯作者：
Paulus W
中科院分区：
文献类型：
--
作者：
Hasselblatt M;Mertsch S;Koos B;Riesmeier B;Stegemann H;Jeibmann A;Tomm M;Schmitz N;Wrede B;Wolff JE;Zheng W;Paulus W
脉络丛乳头状瘤是脑室内乳头状肿瘤，最常发生于儿童和年轻人，其发病机制仍知之甚少。为了确定脉络丛乳头状瘤发展中的有效途径，将从激光显微切割的人脉络丛乳头状瘤细胞（n = 7）获得的基因表达谱与从尸检组织激光显微切割的正常脉络丛上皮细胞（n = 8）进行比较。在DNA微阵列数据分析中，53个探针组在脉络丛乳头状瘤肿瘤细胞中差异表达（>7倍）。使用定量逆转录-PCR证实了TWIST 1、WIF 1、TRPM 3、BCLAF 1和AJAP 1的上调以及IL 6ST的下调。通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物测定和Matrigel测定评估，在大鼠脉络丛上皮细胞系Z310中Twist 1基因表达的敲低显著降低增殖和细胞侵袭，而细胞迁移不受影响。筛选Twist 1敲低后癌症相关基因的表达变化，发现Cdknla、Cflar和Serpinb 2上调，Figf下调。综上所述，利用基因表达谱分析，可以确定几个在人脉络丛乳头状瘤中差异表达的基因。其中，TWIST 1在脉络丛乳头状瘤中高度表达，并促进增殖和侵袭。
The pathogenesis of choroid plexus papillomas, intraventricular papillary neoplasms most often occurring sporadically in children and young adults, remains poorly understood. To identify pathways operative in the development of choroid plexus papillomas, gene expression profiles obtained from laser-microdissected human choroid plexus papilloma cells (n = 7) were compared with that of normal choroid plexus epithelial cells laser microdissected from autopsy tissue (n = 8). On DNA microarray data analysis, 53 probe sets were differentially expressed in choroid plexus papilloma tumor cells (>7-fold). Up-regulation of TWIST1, WIF1, TRPM3, BCLAF1, and AJAP1, as well as down-regulation of IL6ST was confirmed using quantitative reverse transcription-PCR. Knockdown of Twist1 gene expression in the rat choroid plexus epithelial cell line Z310 significantly reduced proliferation as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell invasion in a Matrigel assay, whereas cell migration was not affected. Screening for expressional changes of cancer-related genes upon Twist1 knockdown revealed up-regulation of Cdknla, Cflar, and Serpinb2 and down-regulation of Figf. To conclude, using gene expression profiling, several genes differentially expressed in human choroid plexus papillomas could be identified. Among those, TWIST1 is highly expressed in choroid plexus papillomas and promotes proliferation and invasion.