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Major carcinogenic pathways identified by gene expression analysis of peritoneal mesotheliomas following chemical treatment in F344 rats.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2006 Jul 15; Vol. 214 (2), pp. 144-51. Date of Electronic Publication: 2006 Feb 07. - Publication Year :
- 2006
-
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.
- Subjects :
- Acetates toxicity
Animals
Cell Line
Gene Expression Regulation, Neoplastic drug effects
Insulin-Like Growth Factor I genetics
Integrins genetics
Male
Mesothelioma chemically induced
Mesothelioma pathology
Oligonucleotide Array Sequence Analysis methods
Peritoneal Neoplasms chemically induced
Peritoneal Neoplasms pathology
Rats
Rats, Inbred F344
Reverse Transcriptase Polymerase Chain Reaction methods
Toluene analogs & derivatives
Toluene toxicity
Wnt Proteins genetics
p38 Mitogen-Activated Protein Kinases genetics
Gene Expression Regulation, Neoplastic genetics
Mesothelioma genetics
Peritoneal Neoplasms genetics
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0041-008X
- Volume :
- 214
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 16460773
- Full Text :
- https://doi.org/10.1016/j.taap.2005.12.009