title: Spontaneous mesotheliomas in F344/N rats are characterized by dysregulation of cellular growth and immune function pathways.
abstract: Aged male Fischer 344/N rats are prone to developing spontaneous peritoneal mesotheliomas that arise predominantly from the tunica vaginalis of the testes. A definitive cause for the predominance of this neoplasm in F344/N rats is unknown. Investigation of the molecular alterations that occur in spontaneous rat mesotheliomas may provide insight into their pathogenesis as well enable a better understanding regarding the mechanisms underlying chemically induced mesothelioma in rodents. Mesothelial cell function represents a complex interplay of pathways related to host defense mechanisms and maintenance of cellular homeostasis. Global gene expression profiles of spontaneous mesotheliomas from vehicle control male F344/N rats from 2-year National Toxicology Program carcinogenicity bioassays were analyzed to determine the molecular features of these tumors and elucidate tumor-specific gene expression profiles. The resulting gene expression pattern showed that spontaneous mesotheliomas are associated with upregulation of various growth factors, oncogenes, cytokines, pattern recognition response receptors, and pathogen-associated molecular patterns receptors, and the production of reactive oxygen and nitrogen species, as well as downregulation of apoptosis pathways. Alterations in these pathways in turn trigger molecular responses that stimulate cell proliferation and promote tumor survival and progression.
authors: Integrated Laboratory Systems, Inc., Research Triangle Park, North Carolina, USA.
authors: Pamela E
authors: PE
authors: Blackshear
authors: Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina, USA.
authors: Arun R
authors: AR
authors: Pandiri
authors: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors: Thai-Vu T
authors: TV
authors: Ton
authors: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors: Natasha P
authors: NP
authors: Clayton
authors: Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors: Keith R
authors: KR
authors: Shockley
authors: Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors: Shyamal D
authors: SD
authors: Peddada
authors: Microarray Core, Toxicology and Pharmacology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors: Kevin E
authors: KE
authors: Gerrish
authors: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors: Robert C
authors: RC
authors: Sills
authors: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA hoenerhm@niehs.nih.gov.
authors: Mark J
authors: MJ
authors: Hoenerhoff
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002453:Cell Cycle; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055633:Immune System Phenomena; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D025341:Principal Component Analysis; D051381:Rats; D011916:Rats, Inbred F344; D013736:Testicular Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D013737:Testis / Q000473:pathology; D059467:Transcriptome
keywords: F344/N rat; Fred-PE cells; National Toxicology Program; gene expression; mesothelial cell; mesothelioma; microarray
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