Decreased level of PDCD4 (programmed cell death 4) protein activated cell proliferation in the lung of A/J mouse

Soon Kyung Hwang, Arash Minai-Tehrani, Hwang Tae Lim, Ji Young Shin, Gil Hwan An, Kee Ho Lee, Kee Rang Park, Yeon Soo Kim, George Beck, Hsin Sheng Yang, Myung Haing Cho

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)285-293
Number of pages9
JournalJournal of Aerosol Medicine and Pulmonary Drug Delivery
Volume23
Issue number5
DOIs
StatePublished - Oct 1 2010

Keywords

  • aerosol gene delivery
  • lung cell proliferation
  • shRNA Pdcd4

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmaceutical Science
  • Pharmacology (medical)

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