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

Gene Therapy volume 14, pages 451–458 (2007)Cite this article

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.

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Acknowledgements

This work was partially supported by the grants from the KOSEF (R01-2005-000-10087-0) of the Ministry of Science and Technology in Korea. MHC and SHC were supported by the Nano Systems Institute-National Core Research Center (NSI-NCRC) program of KOSEF. AMT, JSK, JH, SKH, KNY, SJP, DRB are also grateful for the award of the BK21 fellowship. KHL was supported by 21C Frontier Functional Human Genome Project (FG03-0601-003-1-0-0) and National Nuclear R&D Program from Ministry of Science and Technology. GRB was supported by National Cancer Institute Grant CA84573.

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Author notes

  1. A M Tehrani and S-K Hwang: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Toxicology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul, Korea

    A M Tehrani, S-K Hwang, J Hua, W-S Nah, J-T Kwon, J-S Kim, S-H Chang, K-N Yu, S-J Park, D R Bhandari & M-H Cho

  2. Laboratory of Biomedical Polymer and Tissue Engineering, School of Agricultural Biotechnology, Seoul National University, Seoul, Korea

    T-H Kim & C-S Cho

  3. Laboratory of Molecular Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea

    K-H Lee

  4. Department of Food Science & Technology, Chungnam National University, Taejeon, Korea

    G-H An

  5. Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA

    G R Beck Jr

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  1. A M Tehrani
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Correspondence to M-H Cho.

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Tehrani, A., Hwang, SK., Kim, TH. et al. Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice. Gene Ther 14, 451–458 (2007). https://doi.org/10.1038/sj.gt.3302879

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