Back to Search
Start Over
Gene expression studies demonstrate that the K-ras/Erk MAP kinase signal transduction pathway and other novel pathways contribute to the pathogenesis of cumene-induced lung tumors.
- Source :
-
Toxicologic pathology [Toxicol Pathol] 2008 Jul; Vol. 36 (5), pp. 743-52. Date of Electronic Publication: 2008 Jul 22. - Publication Year :
- 2008
-
Abstract
- National Toxicology Program (NTP) inhalation studies demonstrated that cumene significantly increased the incidence of alveolar/bronchiolar adenomas and carcinomas in B6C3F1 mice. Cumene or isopropylbenzene is a component of crude oil used primarily in the production of phenol and acetone. The authors performed global gene expression analysis to distinguish patterns of gene regulation between cumene-induced tumors and normal lung tissue and to look for patterns based on the presence or absence of K-ras and p53 mutations in the tumors. Principal component analysis segregated the carcinomas into groups with and without K-ras mutations, but failed to separate the tumors based on p53 mutation status. Expression of genes associated with the Erk MAP kinase signaling pathway was significantly altered in carcinomas with K-ras mutations compared to tumors without K-ras mutations or normal lung. Gene expression analysis also suggested that cumene-induced carcinomas with K-ras mutations have greater malignant potential than those without mutations. In addition, significance analysis of function and expression (SAFE) demonstrated expression changes of genes regulated by histone modification in carcinomas with K-ras mutations. The gene expression analysis suggested the formation of alveolar/bronchiolar carcinomas in cumene-exposed mice typically involves mutation of K-ras, which results in increased Erk MAP kinase signaling and modification of histones.
- Subjects :
- Adenocarcinoma, Bronchiolo-Alveolar chemically induced
Adenocarcinoma, Bronchiolo-Alveolar genetics
Adenocarcinoma, Bronchiolo-Alveolar pathology
Animals
Female
Gene Expression Regulation, Neoplastic
Immunohistochemistry
Lung Neoplasms pathology
Male
Mice
Mice, Inbred Strains
Signal Transduction physiology
Benzene Derivatives toxicity
Genes, ras genetics
Lung Neoplasms chemically induced
Lung Neoplasms genetics
Mitogen-Activated Protein Kinases metabolism
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1533-1601
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Toxicologic pathology
- Publication Type :
- Academic Journal
- Accession number :
- 18648096
- Full Text :
- https://doi.org/10.1177/0192623308320801