Oncogenes and their interactions in response to environmental chemical exposures

The purpose of this research was to analyze gene x environment (G x E) interactions in lung adenocarcinoma. Based on Oncomine microarray database analysis we showed a higher expression of collagen Type XI Alpha 1 (COL11A1) and reduced expression of Fasciculation and Elongation Protein Zeta 1 (FEZ1) in different stages of lung adenocarcinoma. Using TaqMan quantitative PCR we corroborated the Oncomine microarray data. We demonstrated an increased expression of COL11A1 with 24.65 folds change and under-expression of FEZ1with 0.31fold changes in commercial human lung adenocarcinoma tissues compared to normal lung. Further, by using Comparative Toxicogenomic Database (CTD) we identified 8 strongly interacting environmental chemicals; Thioacetamide > Carbon Tetrachloride> Acetaldehyde> Tetra-chloro dibenzodioxin> Bleomycin> Ethanol> Rosiglitazone> Simvastatin (arranged according to their potency) that caused increase in COL11A1 gene expression. From CTD we also selected 5 chemicals, Nicotine> Alpha-cobratoxin> Tubocurarine> 2',3,3',4',5-pentachloro-4-hydroxybiphenyl> AZM551248 (arranged according to their potency) that strongly interacted to reduce FEZ1 expression. In order to map a common interacting molecular pathway that included higher expression of COL11A1 and under expression of FEZ1 gene we have now selected 66 curated genes on CTD that are co-expressed in response to Nicotine, Thioacetamide and Carbon Tetrachloride exposure. These environmental chemicals are implicated in many environmental and chronic diseases but lung neoplasm was a common denominator for Nicotine, Thioacetamide and Carbon Tetrachloride. In lung neoplasm these three environmental chemicals caused an increase in COL11A1 gene and reduced FEZ1 expression. More experiments are planned to identify signature genes including from the pool of identified 66 co-expressed genes to select those which respond to the selected environmental chemicals with a possibility to determine early stage diagnostic bio-markers for lung adenocarcinoma.