title: Decreased level of PDCD4 (programmed cell death 4) protein activated cell proliferation in the lung of A/J mouse.
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.
  
  
  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.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Soon-Kyung
authors.initials: SK
authors.lastname: Hwang
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Hwang-Tae
authors.initials: HT
authors.lastname: Lim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Shin
authors.forename: Gil-Hwan
authors.initials: GH
authors.lastname: An
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Kee-Rang
authors.initials: KR
authors.lastname: Park
authors.forename: Yeon-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
authors.forename: Hsin-Sheng
authors.initials: HS
authors.lastname: Yang
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: 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
chemical_list: 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
references.citation: Gene Ther. 2007 Dec;14(24):1721-30
references.pmid: 17960162
references.citation: Mol Cancer Ther. 2006 Apr;5(4):1041-9
references.pmid: 16648576
references.citation: Genes Dev. 1999 Jun 15;13(12):1501-12
references.pmid: 10385618
references.citation: Eur J Biochem. 1998 Apr 15;253(2):421-9
references.pmid: 9654092
references.citation: Trends Mol Med. 2003 Jan;9(1):36-41
references.pmid: 12524209
references.citation: Histol Histopathol. 2008 Feb;23(2):227-36
references.pmid: 17999379
references.citation: Cancer Res. 1994 May 1;54(9):2372-7
references.pmid: 8162583
references.citation: Cancer Treat Rev. 2007 Oct;33(6):521-7
references.pmid: 17658220
references.citation: Mol Cell Biol. 1994 Mar;14(3):2077-86
references.pmid: 8114739
references.citation: Oncogene. 2007 Jul 5;26(31):4550-62
references.pmid: 17297470
references.citation: Gene. 1995 Dec 12;166(2):297-301
references.pmid: 8543179
references.citation: J Cell Sci. 2001 Aug;114(Pt 16):2903-10
references.pmid: 11686294
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14037-42
references.pmid: 10570194
references.citation: J Cell Biol. 2004 Nov 8;167(3):399-403
references.pmid: 15533996
references.citation: FEBS Lett. 1998 Dec 4;440(3):419-24
references.pmid: 9872414
references.citation: Cancer Res. 1988 Jun 1;48(11):3112-6
references.pmid: 2835152
references.citation: Am J Physiol Cell Physiol. 2004 Dec;287(6):C1541-6
references.pmid: 15317660
references.citation: Science. 2006 Oct 20;314(5798):467-71
references.pmid: 17053147
references.citation: Mol Cell. 2008 Jun 20;30(6):701-11
references.pmid: 18570873
references.citation: Biochem J. 1999 Dec 1;344 Pt 2:427-31
references.pmid: 10567225
references.citation: Curr Opin Cell Biol. 1997 Dec;9(6):782-7
references.pmid: 9425342
references.citation: Mol Cancer Ther. 2004 Feb;3(2):103-10
references.pmid: 14985450
references.citation: J Biol Chem. 1998 Jun 5;273(23):14484-94
references.pmid: 9603962
references.citation: Nat Rev Cancer. 2004 May;4(5):335-48
references.pmid: 15122205
references.citation: Int J Oncol. 2007 Jul;31(1):19-27
references.pmid: 17549401
references.citation: Cell. 1993 Nov 19;75(4):817-25
references.pmid: 8242752
references.citation: Gene Ther. 2007 Sep;14(18):1353-61
references.pmid: 17611588
references.citation: Mol Cell Biol. 2003 Jan;23(1):26-37
references.pmid: 12482958
references.citation: Exp Cell Res. 1999 Feb 1;246(2):338-47
references.pmid: 9925749
references.citation: Cancer Res. 2006 Jan 1;66(1):315-23
references.pmid: 16397245
references.citation: Cell. 1992 Oct 16;71(2):323-34
references.pmid: 1423597