Effect of 14-3-3 protein induction on oncogenic potential of BEAS-2B bronchial epithelial cells

Molecularly targeted therapies hold promise for many cancers. However, heterogeneity in non-small cell lung cancer (NSCLC) often limits efficacy of targeted therapies to small patient subsets. Oncogenic signalling via EGFR and K-RAS leads to increased cell survival and proliferation, supported by 14-3-3 proteins. Human 14-3-3 proteins are a group of 7 regulator molecules that are increased in up to 60% of NSCLC. Elevated expression of 14-3-3 protein correlates with aggressive disease and poor prognosis. Functionally, 14-3-3 proteins bind to phospho-motif in key signalling proteins resulting in altered function. To evaluate potential role of 14-3-3 proteins in NSCLC initiation and progression, we expressed 14-3-3 in normal cells. Immortalized human bronchial epithelial cells, BEAS-2B, were transduced with lentivirus encoding individual 14-3-3 isoforms. Transduced cells were subjected to liquid and soft-agar colony formation assays. The influence of 14-3-3 protein induction on cell proliferation and survival signalling was assessed. Anchorage dependent colonies of BEAS-2B cells were observed after 7 days. Cells expressing elevated 14-3-3 epsilon were significantly (p We have shown that increased expression of 14-3-3 isoforms in normal airway cells supports colony formation indicative of enhanced cell survival and proliferation signalling, suggesting that 14-3-3 protein expression may play a role in lung cancer initiation and warrants further investigation as a potential therapeutic target.