Gene expression profiles of normal human lung cells affected by adenoviral E1B

2006 
2993 Adenoviruses with deletion of E1B gene can selectively replicate in cancer cells. The underlying mechanisms in tumor selective replication of E1B-deleted adenoviruses are insufficiently understood. Identifying genes with altered expression patterns caused by the E1B proteins in virus-infected cells will further increase our understanding of E1B functions and provide insight into the tumor-selective replication of E1B-mutated adenoviruses on the molecular level. An approach based on large-scale gene array was applied to analyze molecular changes affected by viral E1B. We identified a total of 345 genes with expression changes of two-fold or greater affected by wild-type adenovirus compared with its E1B-deleted counterpart. E1B proteins affect the expression of a diverse range of genes, including CDC25A and cyclin E involved in cell cycle regulation, BCL-2 in apoptosis, heat shock 70K protein in stress responses, and vascular endothelial growth factor in angiogenesis and transcription. These results were confirmed by quantitative real-time PCR and Western blot. This is the first study of the global profile of gene expression altered by the virus E1B in human lung cells, and the majority of the genes were previously not known to be affected by the E1B proteins. The data presented in this study will lead to more detailed analysis of E1B functions and may also lead to development of new agents and approaches for oncolytic therapy.
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