title: Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma.
abstract: Mitochondrial GTPase mitofusin-2 gene (Mfn2) is a novel gene characterised as a cell proliferation inhibitor. Mfn2 protein over-expression, mediated by an adenovirus, has a significant anti-tumour effect in A548 and HT-29 cells. However, there is no report on the effect of Mfn2 on urinary bladder carcinoma (UBCC). In this study, we sought to investigate the function of Mfn2 in UBCC. Mfn2 expression in 36 paired UBCC samples was investigated by reverse transcription-polymerase chain reaction and Western blot analyses. An adenovirus encoding the complete Mfn2 open reading frame (Ad-Mfn2) was used to infect UBCC cells, and an adenoviral vector encoding green fluorescent protein (Ad-GFP) was used as a control. The effects of Mfn2 on cell-cycle distribution and apoptosis were assessed by flow cytometry and Western blot analyses. The Mfn2 protein showed significantly lower expression in UBCC tissues than nearby non-tumourous tissues. Ad-Mfn2 exhibited a significant anti-tumour effect in T24 and 5,637 cells. Mfn2 overexpression in T24 cells significantly inhibited cell proliferation, by arresting the transition of the cell cycle from the G(1) to S phase, and induced apoptosis by upregulating active caspase-3 and cleaved PARP levels. Mfn2 also induced increased p21 and p27 expression levels, but down-regulated PCNA levels. These findings indicate that Mfn2 is a potential UBCC tumour suppressor gene, which showed significantly lower expression in tumour tissues than adjacent non-tumourous tissues and could promote apoptosis and inhibit the proliferation of UBCC cells. Mfn2 may become an important therapeutic target for treating UBCC.
authors.affiliation: Department of Urology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, People's Republic of China.
authors.forename: Baiye
authors.initials: B
authors.lastname: Jin
authors.forename: Guanghou
authors.initials: G
authors.lastname: Fu
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Cheng
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Lv
authors.forename: Geming
authors.initials: G
authors.lastname: Chen
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D002470:Cell Survival; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D019073:HT29 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
references.citation: Acta Biochim Biophys Sin (Shanghai). 2008 May;40(5):426-36
references.pmid: 18465028
references.citation: Eur Urol. 1997;31(4):464-71
references.pmid: 9187909
references.citation: J Cell Biol. 2003 Jan 20;160(2):189-200
references.pmid: 12527753
references.citation: Clin Biochem. 2004 Jul;37(7):562-71
references.pmid: 15234237
references.citation: Br J Cancer. 2004 Sep 13;91(6):1025-31
references.pmid: 15292937
references.citation: Mol Cancer Ther. 2008 Jan;7(1):222-32
references.pmid: 18202024
references.citation: J Pathol. 2002 Sep;198(1):115-20
references.pmid: 12210071
references.citation: Exp Cell Res. 2001 Mar 10;264(1):148-68
references.pmid: 11237531
references.citation: Clin Chim Acta. 2004 Feb;340(1-2):57-65
references.pmid: 14734196
references.citation: J Cell Biol. 2002 Dec 23;159(6):931-8
references.pmid: 12499352
references.citation: Zhonghua Yi Xue Za Zhi. 1997 Nov;77(11):823-8
references.pmid: 9772475
references.citation: J Urol. 1998 Sep;160(3 Pt 1):645-59
references.pmid: 9720515
references.citation: Eur Urol. 2002 Jan;41(1):15-29
references.pmid: 11999461
references.citation: Nat Cell Biol. 2004 Sep;6(9):872-83
references.pmid: 15322553
references.citation: Endocr Relat Cancer. 2008 Mar;15(1):351-64
references.pmid: 18310301
references.citation: J Urol. 1997 Sep;158(3 Pt 1):801-5
references.pmid: 9258086
references.citation: Scand J Urol Nephrol Suppl. 2008 Sep;(218):12-20
references.pmid: 19054893
references.citation: Cancer Res. 2008 Apr 15;68(8):2551-6
references.pmid: 18413720
references.citation: J Cell Sci. 2003 Aug 1;116(Pt 15):3051-60
references.pmid: 12829735
references.citation: Circ Res. 2007 Nov 26;101(11):1113-22
references.pmid: 17901359
references.citation: Hinyokika Kiyo. 1995 Apr;41(4):253-8
references.pmid: 7785554
references.citation: Nature. 2006 Oct 12;443(7112):658-62
references.pmid: 17035996
references.citation: Urology. 1998 Sep;52(3):398-402
references.pmid: 9730450
references.citation: J Natl Cancer Inst. 1998 Jul 15;90(14):1072-9
references.pmid: 9672255
references.citation: Cell. 2007 May 18;129(4):665-79
references.pmid: 17512402