title: Early gene expression differences in inbred mouse strains with susceptibility to pulmonary adenomas.
abstract: Lung cancer is the most common cause of cancer-related deaths in both men and women, and effective preventatives are rare due to the difficulty of early detection. Specific gene expression signatures have been identified in individuals that already developed lung cancer. To identify if gene expression differences could be detected in individuals before the onset of the disease, we obtained lung tissues for microarray analysis from young, healthy mice of 9 inbred strains with known differences in their susceptibility to spontaneous pulmonary adenomas when aged. We found that the most common differentially expressed genes among all possible 36 strain comparisons showed significant associations with cancer- and inflammation-related processes. Significant expression differences between susceptible and resistant strains were detected for Aldh3a1, Cxcr1 and 7, Dpt, and Nptx1-genes with known cancer-related functions, and Cd209, Cxcr1 and 7, and Plag2g1b-genes with known inflammatory-related functions. Whereas Aldh3a1, Cd209, Dpt, and Pla2g1b had increased expression, Cxcr1 and 7, and Nptx1 had decreased expression in strains susceptible to pulmonary adenomas. Thus, our study shows that expression differences between susceptible and resistant strains can be detected in young and healthy mice without manifestation of pulmonary adenomas and, thus, may provide an opportunity of early detection. Finally, the identified genes have previously been reported for human non-small cell lung cancer suggesting that molecular pathways may be shared between these two cancer types.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Stearns
authors.forename: Clinton L
authors.initials: CL
authors.lastname: Cario
authors.forename: Holly S
authors.initials: HS
authors.lastname: Savage
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.forename: Beverly
authors.initials: B
authors.lastname: Paigen
authors.forename: Annerose
authors.initials: A
authors.lastname: Berndt
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D013045:Species Specificity