Establishing a preclinical model of squamous lung cancer to investigate of novel chemopreventive approaches in high risk individuals with bronchial premalignant lesion

Lung cancer is the leading cause of cancer mortality due to limited diagnosis and interception of disease at its earliest curable stages. We have identified transcriptional alterations in epithelial and immune pathways in human lung squamous premalignant lesions (PMLs). To investigate the molecular alterations identified and test prevention strategies pre-clinical models are required. The carcinogen induced N-nitroso-tris-chloroethylurea (NTCU) mouse model of lung squamous cell carcinoma (LUSC) is a promising model that develops histologically comparable lung PMLs to those that precede LUSC development in humans; however, the associated molecular alterations and immune environment driving PML and LUSC development in this model have not been well characterized. Overall design: To characterize the NTCU model we chose to examine the lesions that developed in 2 strains of mice, SWR/J and A/J, which are sensitive to developing LUSC, as not all mouse strains develop disease with treatment of NTCU. Additionally, we selected mice treated with varying total doses of NTCU ranging from 14-50 umol, where treatments with 40 or 80 mmol/L of NTCU were topically administered for 14-25 weeks. The range of doses allowed for the isolation of RNA from a range of lesions across both strains. We additionally included normal airway from mice treated with vehicle control (acetone).