title: Gene expression profiling in PC12 cells infected with an oncolytic Newcastle disease virus strain.
abstract: Although the oncolytic potential of natural, non-engineered Newcastle disease virus (NDV) isolates are well-known, cellular mechanisms determining NDV sensitivity of tumor cells are poorly understood. The aim of the present study was to look for gene expression changes in PC12 pheochromocytoma cells infected with an attenuated NDV strain that may be related to NDV susceptibility. PC12 cells were infected with the NDV strain MTH-68/H for 12h at a titer corresponding to the IC₅₀ value. Total cytoplasmic RNA samples isolated from control and MTH-68/H-infected cells were analyzed using a rat specific Affymetrix exon chip. Genes with at least 2-fold increase or decrease in their expression were identified. MTH-68/H-induced gene expression changes of 9 genes were validated using quantitative reverse transcriptase PCR. A total of 729 genes were up- and 612 genes were down-regulated in PC12 cells infected with MTH-68/H. Using the DAVID functional annotation clustering tool, the up- and down-regulated genes can be categorized into 176 and 146 overlapping functional gene clusters, respectively. Gene expression changes affecting the most important signaling mechanisms (Toll-like receptor signaling, RIG-I-like receptor signaling, interferon signaling, interferon effector pathways, apoptosis pathways, endoplasmic reticulum stress pathways, cell cycle regulation) are analyzed and discussed in detail in this paper. NDV-induced gene expression changes described in this paper affect several regulatory mechanisms and dozens of putative key proteins that may determine the NDV susceptibility of various tumors. Further characterization of these proteins may identify susceptibility markers to predict the chances of virotherapeutic treatment of human tumors.
authors.affiliation: Department of Medical Biology, University of Pécs Medical School, Pécs, Hungary; Signal Transduction Research Group, János Szentágothai Research Centre, Pécs H-7624, Hungary. Electronic address: andrasbalogh@andrasbalogh.hu.
authors.forename: András
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Department of Medical Biology, University of Pécs Medical School, Pécs, Hungary; Signal Transduction Research Group, János Szentágothai Research Centre, Pécs H-7624, Hungary. Electronic address: batorj@freemail.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Bátor
authors.affiliation: Experimental and Clinical Research Center, Charité Medical Faculty and Max-Delbrück Center for Molecular Medicine, Berlin 13125, Germany. Electronic address: lajos.marko@charite.de.
authors.forename: Lajos
authors.initials: L
authors.lastname: Markó
authors.affiliation: Department of Medical Biology, University of Pécs Medical School, Pécs, Hungary; Signal Transduction Research Group, János Szentágothai Research Centre, Pécs H-7624, Hungary. Electronic address: maria.nemeth@aok.pte.hu.
authors.forename: Mária
authors.initials: M
authors.lastname: Németh
authors.affiliation: Department of Medical Biology, University of Pécs Medical School, Pécs, Hungary; Signal Transduction Research Group, János Szentágothai Research Centre, Pécs H-7624, Hungary. Electronic address: marianna.pap@aok.pte.hu.
authors.forename: Marianna
authors.initials: M
authors.lastname: Pap
authors.affiliation: Department of Medical Biology, University of Pécs Medical School, Pécs, Hungary; Signal Transduction Research Group, János Szentágothai Research Centre, Pécs H-7624, Hungary. Electronic address: gyorgy.setalo.jr@aok.pte.hu.
authors.forename: György
authors.initials: G
authors.lastname: Sétáló
authors.affiliation: Experimental and Clinical Research Center, Charité Medical Faculty and Max-Delbrück Center for Molecular Medicine, Berlin 13125, Germany. Electronic address: dominik.mueller@mdc-berlin.de.
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Müller
authors.affiliation: United Cancer Research Institution, Alexandria 22307, VA, USA. Electronic address: UCRI@aol.com.
authors.forename: Laszlo K
authors.initials: LK
authors.lastname: Csatary
authors.affiliation: Department of Medical Biology, University of Pécs Medical School, Pécs, Hungary; Signal Transduction Research Group, János Szentágothai Research Centre, Pécs H-7624, Hungary. Electronic address: jozsef.szeberenyi@aok.pte.hu.
authors.forename: József
authors.initials: J
authors.lastname: Szeberényi
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009522:Newcastle disease virus / Q000235:genetics / Q000502:physiology*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats
keywords: Apoptosis; Gene expression profiling; Interferon signaling; Oncolytic virus; Virotherapy