Differential Transcriptomic Analysis of Spontaneous Lung Tumors in B6C3F1 Mice: Comparison to Human Non–Small Cell Lung Cancer

• Published in: Toxicologic pathology 2012-12, Vol.40 (8), p.1141-1159
• Main Authors: Pandiri, Arun R., Sills, Robert C., Ziglioli, Vincent, Ton, Thai-Vu T, Hong, Hue–Hua L., Lahousse, Stephanie A., Gerrish, Kevin E., Auerbach, Scott S., Shockley, Keith R., Bushel, Pierre R., Peddada, Shyamal D., Hoenerhoff, Mark J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biomarkers, Tumor - metabolism; Carcinogenicity; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; CXCR4 protein; Data processing; Endocytosis; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immune response; Initiation factors; inositol phosphate; Interleukin 8; Liver; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Metabolism; Mice; Mice, Inbred Strains; Mitochondria; Neoplasm Proteins - metabolism; Non-small cell lung carcinoma; Oligonucleotide Array Sequence Analysis; Phagocytosis; Pneumology; PTEN protein; Reverse Transcriptase Polymerase Chain Reaction; Reviews; RhoA protein; RNA, Messenger - metabolism; Signal transduction; Species Specificity; Toxicology; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1177/0192623312447543

Lung cancer is the leading cause of cancer-related death in people and is mainly due to environmental factors such as smoking and radon. The National Toxicology Program (NTP) tests various chemicals and mixtures for their carcinogenic hazard potential. In the NTP chronic bioassay using B6C3F1 mice, the incidence of lung tumors in treated and control animals is second only to the liver tumors. In order to study the molecular mechanisms of chemically induced lung tumors, an understanding of the genetic changes that occur in spontaneous lung (SL) tumors from untreated control animals is needed. The authors have evaluated the differential transcriptomic changes within SL tumors compared to normal lungs from untreated age-matched animals. Within SL tumors, several canonical pathways associated with cancer (eukaryotic initiation factor 2 signaling, RhoA signaling, PTEN signaling, and mammalian target of rapamycin signaling), metabolism (Inositol phosphate metabolism, mitochondrial dysfunction, and purine and pyramidine metabolism), and immune responses (FcγR-mediated phagocytosis, clathrin-mediated endocytosis, interleukin 8 signaling, and CXCR4 signaling) were altered. Meta-analysis of murine SL tumors and human non–small cell lung cancer transcriptomic data sets revealed a high concordance. These data provide important information on the differential transcriptomic changes in murine SL tumors that will be critical to our understanding of chemically induced lung tumors and will aid in hazard analysis in the NTP 2-year carcinogenicity bioassays.