title: Role of B lymphoma Mo-MLV insertion region 1 in the oncogenic behavior of retinoblastomas.
abstract: OBJECTIVE
  This study investigated the relationship between B lymphoma Mo-MLV insertion region 1 (BMI-1)--a polycomb protein for stem cell self-renewal and proliferation--and the clinicopathological parameters of human retinoblastomas, including differentiation status and retinal tissue invasion, as well as the effects of BMI-1 on retinoblastoma Y79 cells.
  
  
  METHODS
  Thirty-four archived human retinoblastoma samples were recruited for BMI-1 immunohistochemistry. The percentage of BMI-1-expressing cells was scored by independent pathologists and the data were correlated with the clinical features. Y79 cells were transfected to overexpress or specifically inhibit BMI-1 for cell proliferation, propidium iodide cell cycle and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis analyses, multicellular sphere formation assay, and gene expression study.
  
  
  RESULTS
  BMI-1 was widely expressed in human retinoblastomas. Higher percentages of BMI-1-expressing cells were selectively limited to undifferentiated tumors and those tumors undergoing invasion to the optic nerve and choroid. However, there was no difference in BMI-1 expression in retinoblastoma retinas with or without tumor invasion. In Y79 cells, BMI-1 stimulated cell proliferation and suppressed apoptosis with reduced p14ARF and p16INK4 expression, along with upregulation of proliferating cell nuclear antigens cyclin D1 and D2. In contrast, silencing BMI-1 reversed these changes. It also upregulated CHX10 and Rx, but not other retinal development-related genes, including nestin and neurofilament M.
  
  
  CONCLUSIONS
  Our work indicates that BMI-1 might render important oncogenic property of retinoblastomas and it could be a therapeutic target for the cancer treatment.
authors.affiliation: Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Ruojin
authors.initials: R
authors.lastname: Ren
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: David Tai Li
authors.initials: DT
authors.lastname: Liu
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.forename: Jitong
authors.initials: J
authors.lastname: Shi
authors.forename: Junyang
authors.initials: J
authors.lastname: Zhao
authors.forename: Bowen
authors.initials: B
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
authors.forename: Carol L
authors.initials: CL
authors.lastname: Shields
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Gary Hin Fai
authors.initials: GH
authors.lastname: Yam
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D002675:Child, Preschool; D003710:Demography; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D013194:Staining and Labeling
chemical_list: C069077:BMI1 protein, human; D063150:Polycomb Repressive Complex 1
references.citation: Curr Opin Ophthalmol. 2009 Sep;20(5):351-5
references.pmid: 19587599
references.citation: Genes Dev. 2006 Aug 1;20(15):2110-20
references.pmid: 16882984
references.citation: Mol Vis. 2007 Jun 08;13:823-32
references.pmid: 17615543
references.citation: Cell Stem Cell. 2010 Dec 3;7(6):682-93
references.pmid: 21112563
references.citation: Mol Vis. 2005 Sep 12;11:729-37
references.pmid: 16179903
references.citation: Int J Cancer. 2007 Nov 15;121(10):2125-31
references.pmid: 17565741
references.citation: Cancer Res. 2010 Jul 1;70(13):5528-38
references.pmid: 20530672
references.citation: Eur Urol. 2007 Aug;52(2):455-63
references.pmid: 17134822
references.citation: Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1506-14
references.pmid: 19029022
references.citation: Cancer Res. 2006 Jun 15;66(12):6063-71
references.pmid: 16778178
references.citation: Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3404-9
references.pmid: 15452042
references.citation: Cancer Sci. 2010 Jul;101(7):1754-60
references.pmid: 20426791
references.citation: Cancer Control. 2004 Sep-Oct;11(5):317-27
references.pmid: 15377991
references.citation: Nature. 2003 May 15;423(6937):255-60
references.pmid: 12714970
references.citation: Oncogene. 2006 Aug 28;25(38):5233-43
references.pmid: 16936742
references.citation: Cancer Cell. 2004 Jun;5(6):539-51
references.pmid: 15193257
references.citation: Nature. 2006 Nov 2;444(7115):61-6
references.pmid: 17080083
references.citation: Nature. 2004 Mar 18;428(6980):337-41
references.pmid: 15029199
references.citation: Neuropathol Appl Neurobiol. 2008 Oct;34(5):555-63
references.pmid: 18346113
references.citation: Invest Ophthalmol Vis Sci. 2002 May;43(5):1344-9
references.pmid: 11980845
references.citation: Breast. 2004 Oct;13(5):383-8
references.pmid: 15454193
references.citation: Cancer Res. 2006 Jun 15;66(12):6225-32
references.pmid: 16778197
references.citation: Am J Pathol. 2007 Apr;170(4):1370-8
references.pmid: 17392175
references.citation: BMC Genet. 2005 Nov 04;6:53
references.pmid: 16269091
references.citation: Br J Cancer. 2010 Mar 2;102(5):892-7
references.pmid: 20145620
references.citation: Clin Cancer Res. 2006 Dec 1;12(23):6929-36
references.pmid: 17145810
references.citation: Cancer Lett. 2004 Jan 20;203(2):217-24
references.pmid: 14732230
references.citation: Am J Pathol. 2010 Jul;177(1):424-35
references.pmid: 20508032
references.citation: Virchows Arch. 2011 Jul;459(1):31-9
references.pmid: 21638011
references.citation: Hum Pathol. 2009 Sep;40(9):1304-11
references.pmid: 19386347
references.citation: Genes Dev. 2005 Jun 15;19(12):1432-7
references.pmid: 15964994
references.citation: Neoplasia. 2005 Mar;7(3):200-6
references.pmid: 15799820
references.citation: Cell. 2009 Jun 12;137(6):1018-31
references.pmid: 19524506
references.citation: Cell. 1991 May 31;65(5):737-52
references.pmid: 1904008
references.citation: Int J Gynecol Cancer. 2010 Dec;20(9):1597-603
references.pmid: 21370603
references.citation: Ann Oncol. 2007 Oct;18(10):1722-33
references.pmid: 17804472
references.citation: Eur J Cancer. 2007 Jul;43(10):1596-603
references.pmid: 17543516
references.citation: J Cancer Res Clin Oncol. 2008 May;134(5):535-41
references.pmid: 17917742
references.citation: Nature. 1999 Jan 14;397(6715):164-8
references.pmid: 9923679
references.citation: Curr Opin Hematol. 2010 Jul;17(4):294-9
references.pmid: 20308890
references.citation: Hum Mol Genet. 2008 May 15;17(10):1363-72
references.pmid: 18211953
references.citation: Hum Mutat. 2002 Nov;20(5):408
references.pmid: 12402348