Widespread expression of thioredoxin and thioredoxin reductase in non-small cell lung carcinoma

We investigated the expression of thioredoxin (Trx) and thioredoxin reducta se (TrxR) in 89 non-small cell lung carcinomas, Additionally, immortalized human bronchial epithelial cells (BEAS 2B) and four human lung carcinoma ce lls lines (A549, SK-MES-1, CALU-6, and A427) were studied by Western blot a nd reverse transcription-PCR for the synthesis of Trx and TrxR protein and mRNA expression in vitro. The histological samples were also studied for im munohistochemical p53 and proliferating cell nuclear antigen expression and apoptosis, In non-neoplastic lung, Trx and TrxR expression was seen in bro nchial epithelial cells and alveolar macrophages, metaplastic alveolar epit helial cells, and chondrocytes of the bronchus, In non-small cell lung carc inomas, there was a widespread expression of Trx and TrxR with only three a nd eight cases negative, respectively. Trx and TrxR expression was located in both cytoplasmic and nuclear compartments of the cells, There was a stat istical association between cytoplasmic and nuclear Trx or TrxR expression. Grade I-II tumors shelved stronger cytoplasmic and nuclear Trx and TrxR im munoreactivity than grade III tumors. No association was found between p53 and proliferating cell nuclear antigen expression and Trx or TrxR immunorea ctivity, However, apoptosis was inversely associated with nuclear Trx and T rxR positivity, In the cell Lines studied, both non-neoplastic BEAS 2B cell s and all of the carcinoma cell Lines expressed Trx and TrxR proteins and m RNA. The results show that these redox-regulating proteins are highly expre ssed in lung carcinomas taking part in activation of transcriptional factor s and regulation of apoptosis in non-small cell lung carcinoma. In high-gra de tumors, Trx and TrxR expression is diminished, suggesting loss of redox regulation in tumors with low differentiation.