TY - JOUR
T1 - Decreased level of PDCD4 (programmed cell death 4) protein activated cell proliferation in the lung of A/J mouse
AU - Hwang, Soon Kyung
AU - Minai-Tehrani, Arash
AU - Lim, Hwang Tae
AU - Shin, Ji Young
AU - An, Gil Hwan
AU - Lee, Kee Ho
AU - Park, Kee Rang
AU - Kim, Yeon Soo
AU - Beck, George
AU - Yang, Hsin Sheng
AU - Cho, Myung Haing
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
KW - aerosol gene delivery
KW - lung cell proliferation
KW - shRNA Pdcd4
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U2 - 10.1089/jamp.2009.0778
DO - 10.1089/jamp.2009.0778
M3 - Article
C2 - 20455770
AN - SCOPUS:77958149807
SN - 1941-2711
VL - 23
SP - 285
EP - 293
JO - Journal of Aerosol Medicine and Pulmonary Drug Delivery
JF - Journal of Aerosol Medicine and Pulmonary Drug Delivery
IS - 5
ER -