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.
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 humancancer. The majority of tumor suppressors are mutationally inactivated, but the expression of Pdcd4 is downregulated with progression in a number of humancancer 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.
Authors: Hsin-Sheng Yang; Aaron P Jansen; Anton A Komar; Xiaojing Zheng; William C Merrick; Sylvain Costes; Stephen J Lockett; Nahum Sonenberg; Nancy H Colburn Journal: Mol Cell Biol Date: 2003-01 Impact factor: 4.272
Authors: J L Cmarik; H Min; G Hegamyer; S Zhan; M Kulesz-Martin; H Yoshinaga; S Matsuhashi; N H Colburn Journal: Proc Natl Acad Sci U S A Date: 1999-11-23 Impact factor: 11.205
Authors: Yuanyuan Wu; Liwen Hu; Yan Liang; Juan Li; Kai Wang; Xuedan Chen; Hui Meng; Xingying Guan; Kang Yang; Yun Bai Journal: Mol Cancer Date: 2017-08-30 Impact factor: 27.401