%0 Journal Article
%T Genes Associated With Prognosis After Surgery For Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro
%A Gavin J Gordon
%A Raphael Bueno
%A David J Sugarbaker
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-169
%X We conducted a high-throughput RNA inhibition screen to knockdown gene expression levels of the four genes comprising the test (ARHGDIA, COBLL1, PKM2, TM4SF1) in both a human lung-derived normal and a tumor cell line using three different small inhibitory RNA molecules per gene. Successful knockdown was confirmed using quantitative RT-PCR. Detection of statistically significant changes in apoptosis and mitosis was performed using immunological assays and quantified using video-assisted microscopy at a single time-point. Changes in nuclear shape, size, and numbers were used to provide additional support of initial findings. Each experiment was conducted in triplicate. Specificity was assured by requiring that at least 2 different siRNAs produced the observed change in each cell line/time-point/gene/assay combination.Knockdown of ARHGDIA, COBLL1, and TM4SF1 resulted in 2- to 4-fold increased levels of apoptosis in normal cells (ARHGDIA only) and tumor cells (all three genes). No statistically significant changes were observed in apoptosis after knockdown of PKM2 or for mitosis after knockdown of any gene.We provide evidence that ARHGDIA, COBLL1, and TM4SF1 are negative regulators of apoptosis in cultured tumor cells. These genes, and their related intracellular signaling pathways, may represent potential therapeutic targets in mesothelioma.Malignant pleural mesothelioma (MPM) is a highly lethal pleural cancer for which there are few effective treatments and overall >90% five-year mortality. Approximately 3,000 patients are diagnosed with MPM in the US annually and the incidence worldwide is projected to rise substantially[1-3] owing to a lack of regulatory oversight governing the use of asbestos, the most common cause for MPM (70-80%) [4-8].MPM is characterized by multi-focal tumor growth originating in the parietal pleura and often accompanied by a pleural effusion. The tumor eventually spreads to involve the visceral pleura producing a rind that constricts the lung,
%K mesothelioma
%K Cell biology/culture
%K Genes/polymorphisms
%K Genetics/genomics
%U http://www.biomedcentral.com/1471-2407/11/169