Data from TWIST-1 Is Overexpressed in Neoplastic Choroid Plexus Epithelial Cells and Promotes Proliferation and Invasion

Abstract

<div>Abstract<p>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 (<i>n</i> = 7) were compared with that of normal choroid plexus epithelial cells laser microdissected from autopsy tissue (<i>n</i> = 8). On DNA microarray data analysis, 53 probe sets were differentially expressed in choroid plexus papilloma tumor cells (>7-fold). Up-regulation of <i>TWIST1, WIF1, TRPM3, BCLAF1</i>, and <i>AJAP1,</i> as well as down-regulation of <i>IL6ST</i> was confirmed using quantitative reverse transcription-PCR. Knockdown of <i>Twist1</i> 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 <i>Twist1</i> knockdown revealed up-regulation of <i>Cdkn1a, Cflar</i>, and <i>Serpinb2</i> and down-regulation of <i>Figf</i>. To conclude, using gene expression profiling, several genes differentially expressed in human choroid plexus papillomas could be identified. Among those, <i>TWIST1</i> is highly expressed in choroid plexus papillomas and promotes proliferation and invasion. [Cancer Res 2009;69(6):2219–23]</p></div>