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Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice

Gene Therapy volume 14, pages 1353–1361 (2007)Cite this article

Abstract

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor 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 was supported by the Nano Systems Institute-National Core Research Center (NSI-NCRC) program of KOSEF. SKH, JH, THK 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 Jr was supported by National Cancer Institute Grant CA84573.

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Authors and Affiliations

  1. Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea

    S-K Hwang, H Jin, J T Kwon, S-H Chang & 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. Laboratory of Cancer Prevention, National Cancer Institute, Frederick, MD, USA

    M R Young & N H Colburn

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

    G R Beck Jr

  6. Graduate Center for Toxicology/Markey Cancer Center, College of Medicine, University of Kentucky, Lexington, KY, USA

    H-S Yang

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  1. S-K Hwang
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  10. G R Beck Jr
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  11. H-S Yang
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  12. M-H Cho
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Correspondence to M-H Cho.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Hwang, SK., Jin, H., Kwon, J. et al. Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice. Gene Ther 14, 1353–1361 (2007). https://doi.org/10.1038/sj.gt.3302983

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