title: Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1.
abstract: BACKGROUND
  Leucine zipper/EF hand-containing transmembrane-1 (LETM1) encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. However, a previous study demonstrated that LETM1 served as an anchor protein for complex formation between mitochondria and ribosome, and regulated mitochondrial biogenesis.
  
  
  RESULTS
  Therefore, we examine the possibility that LETM1 may function to regulate mitochondria and lung tumor growth. In this study, we addressed this question by studying in the effect of adenovirus-mediated LETM1 in the lung cancer cell and lung cancer model mice. To investigate the effects of adenovirus-LETM1 in vitro, we infected with adenovirus-LETM1 in A549 cells. Additionally, in vivo effects of LETM1 were evaluated on K-ras(LA1) mice, human non-small cell lung cancer model mice, by delivering the LETM1 via aerosol through nose-only inhalation system. The effects of LETM1 on lung cancer growth and AMPK related signals were evaluated. Adenovirus-mediated overexpression of LETM1 could induce destruction of mitochondria of lung cancer cells through depleting ATP and AMPK activation. Furthermore, adenoviral-LETM1 also altered Akt signaling and inhibited the cell cycle while facilitating apoptosis. Theses results demonstrated that adenovirus-LETM1 suppressed lung cancer cell growth in vitro and in vivo.
  
  
  CONCLUSIONS
  Adenovirus-mediated LETM1 may provide a useful target for designing lung tumor prevention and treatment.
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: Longzhen
authors.initials: L
authors.lastname: Piao
authors.forename: Hwang-Tae
authors.initials: HT
authors.lastname: Lim
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Kyeong-Nam
authors.initials: KN
authors.lastname: Yu
authors.forename: Youn-Cheol
authors.initials: YC
authors.lastname: Ha
authors.forename: Chan-Hee
authors.initials: CH
authors.lastname: Chae
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009385:Neoplastic Processes; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C488528:LETM1 protein, human; C000594750:LETM1 protein, mouse; D008565:Membrane Proteins
references.citation: Trends Biochem Sci. 2004 Jan;29(1):18-24
references.pmid: 14729328
references.citation: Science. 2006 Jun 16;312(5780):1650-3
references.pmid: 16728594
references.citation: Am J Respir Crit Care Med. 2008 Jul 1;178(1):60-73
references.pmid: 18310482
references.citation: Am J Respir Crit Care Med. 2009 Jun 15;179(12):1131-40
references.pmid: 19286625
references.citation: J Biol Chem. 2002 Jul 5;277(27):23977-80
references.pmid: 11997383
references.citation: Annu Rev Genet. 2005;39:359-407
references.pmid: 16285865
references.citation: Cell Death Differ. 2003 Aug;10(8):870-80
references.pmid: 12867994
references.citation: J Cell Biol. 2006 Feb 13;172(4):553-64
references.pmid: 16476776
references.citation: Bioessays. 2001 Dec;23(12):1112-9
references.pmid: 11746230
references.citation: Dev Cell. 2005 Dec;9(6):843-54
references.pmid: 16326395
references.citation: Curr Biol. 2006 Jul 25;16(14):R551-60
references.pmid: 16860735
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11567-72
references.pmid: 16864783
references.citation: Methods. 2002 Apr;26(4):317-26
references.pmid: 12054922
references.citation: Cell Metab. 2005 Jan;1(1):15-25
references.pmid: 16054041
references.citation: Biol Pharm Bull. 2006 Sep;29(9):1962-5
references.pmid: 16946518
references.citation: Gene Ther. 2007 Dec;14(24):1721-30
references.pmid: 17960162
references.citation: Am J Med Genet. 2001 Apr 1;99(4):338-42
references.pmid: 11252005
references.citation: Cell Signal. 2009 May;21(5):767-77
references.pmid: 19168126
references.citation: Genes Dev. 2001 Nov 15;15(22):2922-33
references.pmid: 11711427
references.citation: Genes Cells. 2003 Jan;8(1):65-79
references.pmid: 12558800
references.citation: Mol Cancer Ther. 2006 Apr;5(4):1041-9
references.pmid: 16648576
references.citation: Biomaterials. 2009 Oct;30(29):5844-52
references.pmid: 19640582
references.citation: Mol Cell Biol. 2006 Jan;26(1):63-76
references.pmid: 16354680
references.citation: J Biol Chem. 2000 Dec 15;275(50):39474-81
references.pmid: 10982793
references.citation: Cell Cycle. 2008 Jun 15;7(12):1782-7
references.pmid: 18583942
references.citation: Cell. 2003 Feb 21;112(4):481-90
references.pmid: 12600312
references.citation: J Natl Cancer Inst. 2006 Jun 21;98(12):846-55
references.pmid: 16788158
references.citation: Biochem J. 2007 Apr 1;403(1):139-48
references.pmid: 17147517
references.citation: J Cell Sci. 2004 Nov 1;117(Pt 23):5479-87
references.pmid: 15509864
references.citation: Cancer Res. 2007 Dec 15;67(24):11630-9
references.pmid: 18089792
references.citation: Trends Mol Med. 2004 Aug;10(8):372-8
references.pmid: 15310457
references.citation: Curr Drug Deliv. 2006 Jan;3(1):55-63
references.pmid: 16472094
references.citation: Biochim Biophys Acta. 2004 Dec 10;1705(1):43-51
references.pmid: 15585172
references.citation: Biochem Pharmacol. 2005 Jul 1;70(1):1-12
references.pmid: 15907809
references.citation: Cancer Res. 2004 Nov 1;64(21):7971-6
references.pmid: 15520204
references.citation: Mitochondrion. 2002 May;1(5):425-35
references.pmid: 16120295
references.citation: Mol Cell. 2005 Apr 29;18(3):283-93
references.pmid: 15866171
references.citation: Oncogene. 2009 May 7;28(18):1993-2002
references.pmid: 19347029
references.citation: Cell. 2006 Feb 10;124(3):471-84
references.pmid: 16469695