Nuclear Factor kappa B is central to Marek's Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

Persistent Link:
http://hdl.handle.net/10150/610102
Title:
Nuclear Factor kappa B is central to Marek's Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo
Author:
Kumar, Shyamesh; Kunec, Dusan; Buza, Joram; Chiang, Hsin-I; Zhou, Huaijun; Subramaniam, Sugalesini; Pendarvis, Ken; Cheng, Hans; Burgess, Shane
Affiliation:
Department of Pathobiology and Population Medicine, Mississippi State University, PO Box 6100, MS, Mississippi State, 39762, USA; Institut für Virologie, Freie Universität Berlin, Berlin, Germany; School of Life Sciences and Bioengineering, Nelson Mandela African Institute of Science and Technology, PO Box 447, Arusha, Tanzania; Department of Bioengineering, University of California-San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA; Department of Poultry Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX, 77843, USA; Comparative Medicine and Integrative Biology Graduate Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA; College of Agriculture and Life Sciences, University of Arizona, P.O. Box 210036, Tucson, AZ, 85721, USA; USDA-ARS, Avian Disease and Oncology Laboratory, 4279 East Mount Hope Road, East Lansing, MI, 48823, USA
Issue Date:
2012
Publisher:
BioMed Central
Citation:
Kumar et al. BMC Systems Biology 2012, 6:123 http://www.biomedcentral.com/1752-0509/6/123
Journal:
BMC Systems Biology
Rights:
© 2012 Kumar et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:Marek's Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the non-neoplastic cells (CD30lo) form the majority of population. MD is a unique natural in-vivo model of human CD30hi lymphomas with both natural CD30hi lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic transformation from CD30lo expressing phenotype to CD30hi expressing neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems Biology modeling; we compare the global gene expression of CD30lo and CD30hi cells to identify key pathways of neoplastic transformation. We propose and test a specific mechanism of neoplastic transformation, and genetic resistance, involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B (NF-kappaB) family and CD30; we also identify a novel Meq protein interactome.RESULTS:Our results show that a) CD30lo lymphocytes are pre-neoplastic precursors and not merely reactive lymphocytes; b) multiple transformation mechanisms exist and are potentially controlled by Meq; c) Meq can drive a feed-forward cycle that induces CD30 transcription, increases CD30 signaling which activates NF-kappaB, and, in turn, increases Meq transcription; d) Meq transcriptional repression or activation of the CD30 promoter generally correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with proteins involved in physiological processes central to lymphomagenesis.CONCLUSIONS:In the context of the MD lymphoma microenvironment (and potentially in other CD30hi lymphomas as well), our results show that the neoplastic transformation is a continuum and the non-neoplastic cells are actually pre-neoplastic precursor cells and not merely immune bystanders. We also show that NF-kappaB is a central player in MDV induced neoplastic transformation of CD30-expressing lymphocytes in vivo. Our results provide insights into molecular mechanisms of neoplastic transformation in MD specifically and also herpesvirus induced lymphoma in general.
EISSN:
1752-0509
DOI:
10.1186/1752-0509-6-123
Keywords:
Marek's disease; Lymphomas; Meq; NF-κB; Genetic resistance; CD30; Proteomics
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1752-0509/6/123

Full metadata record

DC FieldValue Language
dc.contributor.authorKumar, Shyameshen
dc.contributor.authorKunec, Dusanen
dc.contributor.authorBuza, Joramen
dc.contributor.authorChiang, Hsin-Ien
dc.contributor.authorZhou, Huaijunen
dc.contributor.authorSubramaniam, Sugalesinien
dc.contributor.authorPendarvis, Kenen
dc.contributor.authorCheng, Hansen
dc.contributor.authorBurgess, Shaneen
dc.date.accessioned2016-05-20T08:58:37Z-
dc.date.available2016-05-20T08:58:37Z-
dc.date.issued2012en
dc.identifier.citationKumar et al. BMC Systems Biology 2012, 6:123 http://www.biomedcentral.com/1752-0509/6/123en
dc.identifier.doi10.1186/1752-0509-6-123en
dc.identifier.urihttp://hdl.handle.net/10150/610102-
dc.description.abstractBACKGROUND:Marek's Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2en
dc.description.abstractMDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the non-neoplastic cells (CD30lo) form the majority of population. MD is a unique natural in-vivo model of human CD30hi lymphomas with both natural CD30hi lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic transformation from CD30lo expressing phenotype to CD30hi expressing neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems Biology modelingen
dc.description.abstractwe compare the global gene expression of CD30lo and CD30hi cells to identify key pathways of neoplastic transformation. We propose and test a specific mechanism of neoplastic transformation, and genetic resistance, involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B (NF-kappaB) family and CD30en
dc.description.abstractwe also identify a novel Meq protein interactome.RESULTS:Our results show that a) CD30lo lymphocytes are pre-neoplastic precursors and not merely reactive lymphocytesen
dc.description.abstractb) multiple transformation mechanisms exist and are potentially controlled by Meqen
dc.description.abstractc) Meq can drive a feed-forward cycle that induces CD30 transcription, increases CD30 signaling which activates NF-kappaB, and, in turn, increases Meq transcriptionen
dc.description.abstractd) Meq transcriptional repression or activation of the CD30 promoter generally correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with proteins involved in physiological processes central to lymphomagenesis.CONCLUSIONS:In the context of the MD lymphoma microenvironment (and potentially in other CD30hi lymphomas as well), our results show that the neoplastic transformation is a continuum and the non-neoplastic cells are actually pre-neoplastic precursor cells and not merely immune bystanders. We also show that NF-kappaB is a central player in MDV induced neoplastic transformation of CD30-expressing lymphocytes in vivo. Our results provide insights into molecular mechanisms of neoplastic transformation in MD specifically and also herpesvirus induced lymphoma in general.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1752-0509/6/123en
dc.rights© 2012 Kumar et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.subjectMarek's diseaseen
dc.subjectLymphomasen
dc.subjectMeqen
dc.subjectNF-κBen
dc.subjectGenetic resistanceen
dc.subjectCD30en
dc.subjectProteomicsen
dc.titleNuclear Factor kappa B is central to Marek's Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivoen
dc.typeArticleen
dc.identifier.eissn1752-0509en
dc.contributor.departmentDepartment of Pathobiology and Population Medicine, Mississippi State University, PO Box 6100, MS, Mississippi State, 39762, USAen
dc.contributor.departmentInstitut für Virologie, Freie Universität Berlin, Berlin, Germanyen
dc.contributor.departmentSchool of Life Sciences and Bioengineering, Nelson Mandela African Institute of Science and Technology, PO Box 447, Arusha, Tanzaniaen
dc.contributor.departmentDepartment of Bioengineering, University of California-San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USAen
dc.contributor.departmentDepartment of Poultry Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX, 77843, USAen
dc.contributor.departmentComparative Medicine and Integrative Biology Graduate Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USAen
dc.contributor.departmentCollege of Agriculture and Life Sciences, University of Arizona, P.O. Box 210036, Tucson, AZ, 85721, USAen
dc.contributor.departmentUSDA-ARS, Avian Disease and Oncology Laboratory, 4279 East Mount Hope Road, East Lansing, MI, 48823, USAen
dc.identifier.journalBMC Systems Biologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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