novel genes and pathways modulated by syndecan-1 implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells新基因和通路调制syndecan-1对恶性间皮瘤细胞的增殖和细胞循环调节.pdfVIP

Novel Genes and Pathways Modulated by Syndecan-1: Implications for the Proliferation and Cell-Cycle Regulation of Malignant Mesothelioma Cells ¨ ´ 1 1 1 1 1 Tunde Szatmari *, Filip Mundt , Ghazal Heidari-Hamedani , Fang Zong , Elena Ferolla , 2 1 1 Andrey Alexeyenko , Anders Hjerpe , Katalin Dobra 1 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden, 2 Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden Abstract Malignant pleural mesothelioma is a highly malignant tumor, originating from mesothelial cells of the serous cavities. In mesothelioma the expression of syndecan-1 correlates to epithelioid morphology and inhibition of growth and migration. Our previous data suggest a complex role of syndecan-1 in mesothelioma cell proliferation although the exact underlying molecular mechanisms are not completely elucidated. The aim of this study is therefore to disclose critical genes and pathways affected by syndecan-1 in mesothelioma; in order to better understand its importance for tumor cell growth and proliferation. We modulated the expression of syndecan-1 in a human mesothelioma cell line via both overexpression and silencing, and followed the transcriptomic responses with microarray analysis. To project the transcriptome analysis on the full-dimensional picture of cellular regulation, we applied pathway analysis using Ingenuity Pathway Analysis (IPA) and a novel method of network enrichment analysis (NEA) which elucidated signaling relations between differentially expressed genes and pathways acting via various molecular mechanisms. Syndecan-