Molecular targets and biological effects of PAX6 in lung cancer

Abstract

Lung cancer is by far the leading cause of cancer-related mortality worldwide regardless of sex, and has a dismal overall 5-year survival rate of approximately 15%. More than 85% of all lung cancers are non-small cell lung cancer (NSCLC), and about 50% of these are adenocarcinomas. Targeted treatment has shown promising results in treating certain types of NSCLC, but the overall survival is still frustratingly low. PAX6 is a transcription factor that has very recently been shown to have positive effect on survival when expressed in lung cancer. We want to identify potential target genes for PAX6 that can explain this observation, and possibly provide a greater understanding of the molecular mechanisms involved in the pathogenesis of non-small cell lung cancer. PAX6 expression was knocked-down in lung cancer cell lines, and expression of some cancer-associated genes in PAX6-knockdown samples was compared with expression in control samples. Expression was studied on gene level, using comparative qPCR and on protein-level, using western blot. Cell behaviour after PAX6 knockdown was studied in real-time using two different systems designed for this purpose. Our results show that PAX6 does regulate a number of cancer associated genes, and that PAX6 has influence on cell proliferation, migration and apoptosis of lung cancer cell lines.