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Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice

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Authors
Tehrani, A M; Hwang, S-K; Kim, T-H; Cho, C-S; Hua, J; Nah, W-S; Kwon, J-T; Kim, J-S; Chang, S-H; Yu, Kyeong Nam; Park, S-J; Bhandari, DR; Lee, K-H; An, G-H; Beck Jr, GR; Cho, Myung-Haing
Issue Date
2006-10-19
Publisher
Nature Publishing Group
Citation
Gene Ther 2007; 14: 451–458
Keywords
Aktnoninvasive aerosol deliverydual luciferase reporter micelung cancer
Abstract
Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.
ISSN
0969-7128
Language
English
URI
http://hdl.handle.net/10371/6103
DOI
https://doi.org/10.1038/sj.gt.3302879
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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