Genes Associated with Prognosis after Surgery for Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro

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Genes Associated with Prognosis after Surgery for Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro

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dc.contributor.author Sugarbaker, David John
dc.contributor.author Bueno, Raphael
dc.contributor.author Gordon, Gavin J.
dc.date.accessioned 2011-12-07T01:27:10Z
dc.date.issued 2011
dc.identifier.citation Gordon, Gavin J, Raphael Bueno, and David J Sugarbaker. 2011. Genes associated with prognosis after surgery for malignant pleural mesothelioma promote tumor cell survival in vitro. BMC Cancer 11:169. en_US
dc.identifier.issn 1471-2407 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5362749
dc.description.abstract Background: Mesothelioma is an aggressive neoplasm with few effective treatments, one being cytoreductive surgery. We previously described a test, based on differential expression levels of four genes, to predict clinical outcome in prospectively consented mesothelioma patients after surgery. In this study, we determined whether any of these four genes could be linked to a cancer relevant phenotype. Methods: 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. Results: 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. Conclusions: 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. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi://10.1186/1471-2407-11-169 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112160/pdf/ en_US
dash.license LAA
dc.subject mesothelioma en_US
dc.subject cell biology en_US
dc.subject culture en_US
dc.subject genes en_US
dc.subject polymorphisms en_US
dc.subject genetics en_US
dc.subject genomics en_US
dc.title Genes Associated with Prognosis after Surgery for Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal BMC Cancer en_US
dash.depositing.author Sugarbaker, David John
dc.date.available 2011-12-07T01:27:10Z
dash.affiliation.other HMS^Surgery-Brigham and Women's Hospital en_US

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