Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents. Oncotarget 2017 Mar 21;8(12):18885-18900
Date
12/10/2016Pubmed ID
27935865Pubmed Central ID
PMC5386655DOI
10.18632/oncotarget.13806Scopus ID
2-s2.0-85015809993 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
Due to exposure to environmental toxicants, a "field cancerization" effect occurs in the lung resulting in the development of a field of initiated but morphologically normal appearing cells in the damaged epithelium of bronchial airways with dysregulated gene expression patterns. Using a mouse model of lung squamous cell carcinoma (SCC), we performed transcriptome sequencing (RNA-Seq) to profile bronchial airway gene expression and found activation of the PI3K and Myc signaling networks in cytologically normal bronchial airway epithelial cells of mice with preneopastic lung SCC lesions, which was reversed by treatment with the PI3K Inhibitor XL-147 and pioglitazone, respectively. Activated MYC signaling was also present in premalignant and tumor tissues from human lung SCC patients. In addition, we identified a key microRNA, mmu-miR-449c-5p, whose suppression significantly up-regulated Myc expression in the normal bronchial airway epithelial cells of mice with early stage SCC lesions. We developed a novel bronchial genomic classifier in mice and validated it in humans. In the classifier, Ppbp (pro-platelet basic protein) was overexpressed 115 fold in the bronchial airways of mice with preneoplastic lung SCC lesions. This is the first report that demonstrates Ppbp as a novel biomarker in the bronchial airway for lung cancer diagnosis.
Author List
Xiong D, Pan J, Zhang Q, Szabo E, Miller MS, Lubet RA, You M, Wang YMESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers, Tumor
Bronchi
Carcinoma, Squamous Cell
Chemokines, CXC
Chemoprevention
Disease Models, Animal
Gene Expression Profiling
Lung Neoplasms
Mice
Precancerous Conditions
Quinoxalines
Sulfonamides
Thiazolidinediones
Transcriptome
