Gene expression profiles of normal human lung cells affected by adenoviral E1B.
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. The gene array data were confirmed by quantitative real-time PCR and Western blot. E1B proteins affect the expression of a diverse range of genes involved in cell cycle regulation, apoptosis, stress responses and angiogenesis. This is the first study of the global profile of gene expression altered by the viral E1B proteins in human lung cells, and the majority of the genes were previously not known to be affected by the viral 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.
J. Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Xiao-Mei
XM
Rao
Xinyu
X
Zheng
Sabine
S
Waigel
Wolfgang
W
Zacharias
Kelly M
KM
McMasters
Heshan Sam
HS
Zhou
D017501:Adenovirus E1B Proteins / Q000235:genetics*; D004798:Enzymes / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000821:virology*; D009693:Nucleic Acid Hybridization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D017501:Adenovirus E1B Proteins; D004798:Enzymes; D042461:Vascular Endothelial Growth Factor A