title: High-throughput molecular and histopathologic profiling of tumor tissue in a novel transplantable model of murine neuroblastoma: new tools for pediatric drug discovery.
abstract: Using two MYCN transgenic mouse strains, we established 10 transplantable neuroblastoma cell lines via serial orthotopic passage in the adrenal gland. Tissue arrays demonstrate that by histochemistry, vascularity, immunohistochemical staining for neuroblastoma markers, catecholamine analysis, and concurrent cDNA microarray analysis, there is a close correspondence between the transplantable lines and the spontaneous tumors. Several genes closely associated with the pathobiology and immune evasion of neuroblastoma, novel targets that warrant evaluation, and decreased expression of tumor suppressor genes are demonstrated. These studies describe a unique and generalizable approach to expand the utility of transgenic models of spontaneous tumor, providing new tools for preclinical investigation.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Jimmy K
authors.initials: JK
authors.lastname: Stauffer
authors.forename: Rimas J
authors.initials: RJ
authors.lastname: Orentas
authors.forename: Erin
authors.initials: E
authors.lastname: Lincoln
authors.forename: Tahira
authors.initials: T
authors.lastname: Khan
authors.forename: Rosalba
authors.initials: R
authors.lastname: Salcedo
authors.forename: Julie A
authors.initials: JA
authors.lastname: Hixon
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Back
authors.forename: Jun S
authors.initials: JS
authors.lastname: Wei
authors.forename: Rajesh
authors.initials: R
authors.lastname: Patidar
authors.forename: Young
authors.initials: Y
authors.lastname: Song
authors.forename: Laura
authors.initials: L
authors.lastname: Hurd
authors.forename: Maria
authors.initials: M
authors.lastname: Tsokos
authors.forename: Edwin W
authors.initials: EW
authors.lastname: Lai
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: William
authors.initials: W
authors.lastname: Weiss
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.forename: Jon M
authors.initials: JM
authors.lastname: Wigginton
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis; D055808:Drug Discovery; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D000071447:N-Myc Proto-Oncogene Protein; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D025341:Principal Component Analysis; D046888:Tissue Array Analysis
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051358:Cyclin-Dependent Kinase 4