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


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.
Hwang
Soon-Kyung
SK
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Minai-Tehrani
Arash
A
Lim
Hwang-Tae
HT
Shin
Ji-Young
JY
An
Gil-Hwan
GH
Lee
Kee-Ho
KH
Park
Kee-Rang
KR
Kim
Yeon-Soo
YS
Beck
George R
GR
Yang
Hsin-Sheng
HS
Cho
Myung-Haing
MH
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage* / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D015536:Down-Regulation; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D016601:RNA-Binding Proteins / Q000008:administration & dosage* / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C498443:Pdcd4 protein, mouse; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D014568:Urokinase-Type Plasminogen Activator
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