| Gene expression profile in a glioma cell line resistant to cell death induced by the chimeric tumor suppressor-1 (CTS-1), a dominant-positive variant of p53--the role of NFkappaB. | |
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MedLine Citation:
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PMID: 20015865 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The identification of genes involved in carcinogenesis and tumor progression is of great interest since these genes might be feasible as candidates for new tumor-targeted therapy strategies. Chimeric tumor suppressor-1 (CTS-1), an artificial synthetic variant of p53, resists common p53 inactivation and could therefore be defined as a dominant-positive p53 variant. Overexpression of CTS-1 induces caspase-independent cell death. We used whole-genome microarray expression analysis in a parental (229(P)) and a CTS-1-resistant glioma cell line (229(Res)) to analyze alterations in gene expression in Ad-CTS-1-infected and in uninfected parental and resistant cells. In total, 700 genes were differentially expressed in infected and 313 genes in uninfected 229(Res) versus 229(P) cells. Ingenuity Pathway Analysis determined a variety of differentially expressed genes in Ad-CTS-1-infected cells that were members of intracellular networks with central tumor-involved players such as nuclear factor-kappaB (NFkappaB), protein kinase B/AKT or transforming growth factor-beta. Here we focused on the function of NFkappaB in Ad-CTS-1-mediated cell death in glioma. NFkappaB was activated in Ad-CTS-1-infected 229(P) but not 229(Res) cells. NFkappaB activation was accompanied by the induction of cell death in parental cells. Inhibition of NFkappaB activity by expression of an IkappaB super repressor or upregulation of the NFkappaB-linked gene Bex protected parental cells to Ad-CTS-1-induced cell death, whereas knockdown of Bex sensitized both parental and resistant cells. Taken together, these data suggest that activation of the normally antiapoptotic protein NFkappaB does not always necessarily protect cells from apoptosis but, in the glioma cell lines tested so far, and in an environment where p53 is constitutively active, also leads to the induction of cell death. |
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Authors:
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Janina Seznec; Simone Weit; Ulrike Naumann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-16 |
Journal Detail:
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Title: Carcinogenesis Volume: 31 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-05 Completed Date: 2010-04-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 411-8 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Neuro-Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of T?bingen, Otfried-M?ller-Strasse 27, 72076 T?bingen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Apoptosis / physiology* Gene Expression Profiling* Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Genes, Dominant Genes, p53 Genetic Vectors / pharmacology Glioma / pathology* Humans Microarray Analysis NF-kappa B / physiology* Neoplasm Proteins / biosynthesis, genetics, physiology Nerve Tissue Proteins / genetics, physiology Recombinant Fusion Proteins / genetics, physiology Signal Transduction / physiology Tumor Suppressor Protein p53 / physiology* |
| Chemical | |
Reg. No./Substance:
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0/BEX1 protein, human; 0/NF-kappa B; 0/Neoplasm Proteins; 0/Nerve Tissue Proteins; 0/Recombinant Fusion Proteins; 0/Tumor Suppressor Protein p53; 0/chimeric tumor suppressor-1 protein |
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