期刊
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY
卷 23, 期 5, 页码 285-293出版社
MARY ANN LIEBERT INC
DOI: 10.1089/jamp.2009.0778
关键词
aerosol gene delivery; shRNA Pdcd4; lung cell proliferation
资金
- Ministry of Education, Science and Technology in Korea [M10534040001-08N340400110]
- Nano Systems Institute-National Core Research Center (NSI-NCRC) of KOSEF
- 21C Frontier Functional Human Genome Project [FG03-0601-003-1-0-0]
- Ministry of Science and Technology
- National Research Foundation of Korea [2005-2001152] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Background: Programmed cell death 4 (PDCD4), a protein that binds to eukaryotic initiation factor 4A (eIF4A), inhibits the initiation of translation. Although a number of tumor suppressors target transcription, Pdcd4 is the first suppressor targeting protein translation, and has also been suggested to function as a tumor suppressor gene in human cancer. The majority of tumor suppressors are mutationally inactivated, but the expression of Pdcd4 is downregulated with progression in a number of human cancer sites, including the lung. Methods: An aerosol of lentivirus-shRNA Pdcd4 was delivered into A/J mice, through a nose-only inhalation system twice a week for 1 month. Results and Conclusions: Downregulated Pdcd4 resulted in increase levels of antiapoptotic and uPA-regulated proteins. We also found that downregulated Pdcd4 induced the mTOR/p70S6K pathway and cell-cycle proteins. Our results suggest that Pdcd4 may perform a critical function in the regulation of lung cancer cell proliferation.
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