Differential Expression of TOM34, AL1A1, PADI2 and KLRBA in NNK Induced Lung Cancer in Wistar Rats and their Implications

Background: Lung cancer is the most common cancer with a high mortality rate. The diagnosis only at advanced stages and lack of effective treatment are the main factors responsible for high mortality. Tobacco smoke is the major responsible factor for inflammation and tumor development in lungs. Objective: The present study was carried out to identify differentially expressed proteins and elucidate their role in carcinogenesis. Methods: The lung cancer was developed in Wistar rats by using NNK as carcinogen and cancer development was confirmed by histopathological examination. The 2D SDS PAGE was used to analyse total proteins and find out differentially expressed proteins in NNK treated lung tissue vis-a-vis control tissue. The findings of proteomic analysis were further validated by quantification of corresponding transcripts using Real Time PCR. Finally, Cytoscape was used to find out protein-protein interaction. Results: The histopathological examinations showed neoplasia at 9th month after NNK treatment. The proteomic analysis revealed several differentially expressed proteins, four of which were selected for further studies. (TOM34, AL1A1, PADI2 and KLRBA) that were up regulated in NNK treated lung tissue. The real time analysis showed over expression of the genes coding for the selected proteins. Thus, the proteomic and transcriptomic data corroborate each other. Further, these proteins showed interaction with the members of NF-ΚB family and STAT3. Conclusion: We conclude that these proteins play a substantial role in the induction of lung cancer through NF-ΚB and STAT3 pathway. Therefore, these may have the potential to be used as therapeutic targets and for early detection of lung cancer.