title: Major carcinogenic pathways identified by gene expression analysis of peritoneal mesotheliomas following chemical treatment in F344 rats.
abstract: This study was performed to characterize the gene expression profile and to identify the major carcinogenic pathways involved in rat peritoneal mesothelioma (RPM) formation following treatment of Fischer 344 rats with o-nitrotoluene (o-NT) or bromochloracetic acid (BCA). Oligo arrays, with over 20,000 target genes, were used to evaluate o-NT- and BCA-induced RPMs, when compared to a non-transformed mesothelial cell line (Fred-PE). Analysis using Ingenuity Pathway Analysis software revealed 169 cancer-related genes that were categorized into binding activity, growth and proliferation, cell cycle progression, apoptosis, and invasion and metastasis. The microarray data were validated by positive correlation with quantitative real-time RT-PCR on 16 selected genes including igf1, tgfb3 and nov. Important carcinogenic pathways involved in RPM formation included insulin-like growth factor 1 (IGF-1), p38 MAPkinase, Wnt/beta-catenin and integrin signaling pathways. This study demonstrated that mesotheliomas in rats exposed to o-NT- and BCA were similar to mesotheliomas in humans, at least at the cellular and molecular level.
authors.affiliation: Environmental Toxicology Program, National Institute of Environmental Health Sciences, MD B3-08, 111 Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Yongbaek
authors.initials: Y
authors.lastname: Kim
authors.forename: Thai-Vu
authors.initials: TV
authors.lastname: Ton
authors.forename: Anthony B
authors.initials: AB
authors.lastname: DeAngelo
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.forename: Theodora R
authors.initials: TR
authors.lastname: Devereux
authors.forename: Colleen
authors.initials: C
authors.lastname: Anna
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Collins
authors.forename: Richard S
authors.initials: RS
authors.lastname: Paules
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Crosby
authors.forename: Robert C
authors.initials: RC
authors.lastname: Sills
mesh_terms: D000085:Acetates / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D016023:Integrins / Q000235:genetics; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010534:Peritoneal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000235:genetics*; D014050:Toluene / Q000031:analogs & derivatives / Q000633:toxicity; D051153:Wnt Proteins / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: D000085:Acetates; D016023:Integrins; D051153:Wnt Proteins; D014050:Toluene; D007334:Insulin-Like Growth Factor I; C029955:2-nitrotoluene; C099813:bromochloroacetic acid; D048051:p38 Mitogen-Activated Protein Kinases