title: Oxidative stress specifically downregulates survivin to promote breast tumour formation.
abstract: BACKGROUND
  Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood.
  
  
  RESULTS
  DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours.
  
  
  CONCLUSIONS
  Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.
authors: Department of Internal Medicine, Charles Drew University of Medicine and Science, Los Angeles, CA 90059, USA. spervin@mednet.ucla.edu
authors: S
authors: S
authors: Pervin
authors: L
authors: L
authors: Tran
authors: R
authors: R
authors: Urman
authors: M
authors: M
authors: Braga
authors: M
authors: M
authors: Parveen
authors: S A
authors: SA
authors: Li
authors: G
authors: G
authors: Chaudhuri
authors: R
authors: R
authors: Singh
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress / Q000235:genetics*; D011912:Rats, Inbred ACI; D000077022:Survivin; D014183:Transplantation, Heterologous
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6
references: Kaohsiung J Med Sci. 2011 May;27(5):167-72
references: 21527182
references: Neoplasma. 2010;57(6):572-7
references: 20845996
references: J Egypt Natl Canc Inst. 2008 Dec;20(4):348-57
references: 20571593
references: Cancer Res. 2001 Jun 15;61(12):4701-6
references: 11406540
references: Surg Oncol. 2012 Jun;21(2):125-31
references: 21334875
references: Antioxid Redox Signal. 2012 Jun 1;16(11):1229-47
references: 22229841
references: Endocrinology. 2009 Mar;150(3):1259-68
references: 18948405
references: Trends Endocrinol Metab. 2009 Sep;20(7):332-40
references: 19733481
references: Breast Cancer Res Treat. 2002 Dec;76(3):221-36
references: 12462383
references: Cell Signal. 2012 May;24(5):981-90
references: 22286106
references: Histopathology. 2011 May;58(6):854-62
references: 21585424
references: Breast Cancer Res Treat. 2012 Jun;133(3):881-8
references: 22048816
references: Carcinogenesis. 2009 May;30(5):777-84
references: 19255063
references: Cancer Biol Ther. 2005 Dec;4(12):1367-73
references: 16294028
references: Int J Mol Med. 2012 Mar;29(3):485-90
references: 22109572
references: FEBS J. 2008 Jul;275(13):3249-77
references: 18513324
references: Aging Dis. 2011 Jun;2(3):219-30
references: 22396874
references: J Biol Chem. 2010 Feb 12;285(7):4481-8
references: 20018867
references: Endocrinology. 2006 Jan;147(1):141-54
references: 16210377
references: Drug Discov Today. 2011 Jun;16(11-12):485-94
references: 21511051
references: Cancer Res. 2008 Jun 15;68(12):4862-74
references: 18559534
references: EMBO Mol Med. 2010 Jun;2(6):211-30
references: 20535745
references: Apoptosis. 2011 Apr;16(4):347-58
references: 21190085
references: J Clin Invest. 2001 Oct;108(7):981-90
references: 11581299
references: Carcinogenesis. 2004 Jan;25(1):3-9
references: 14514655
references: Cancer Res. 2003 Dec 15;63(24):8853-60
references: 14695202
references: J Carcinog. 2011;10:35
references: 22279420
references: Adv Anat Pathol. 2012 Jan;19(1):39-53
references: 22156833
references: Cancer Res. 2004 May 15;64(10):3580-5
references: 15150115
references: Horm Cancer. 2010 Feb;1(1):34-43
references: 21761349
references: Clin Cancer Res. 2011 Oct 1;17(19):6125-9
references: 21685479
references: Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18123-8
references: 15601761
references: J Clin Invest. 2011 Oct;121(10):3786-8
references: 21965334
references: Curr Pharm Des. 2010;16(4):451-62
references: 20236074
references: Adv Exp Med Biol. 2003;532:195-207
references: 12908558
references: J Biol Chem. 2007 Jun 15;282(24):17640-8
references: 17435218
references: Nanomedicine. 2011 Dec;7(6):904-13
references: 21664489
references: Cancer Res. 2003 Sep 1;63(17):5470-9
references: 14500383
references: Cold Spring Harb Perspect Biol. 2011 Feb 01;3(2):
references: 21047916
references: Oncogene. 2002 Oct 31;21(50):7700-9
references: 12400012
references: Cancer Biol Ther. 2006 Jul;5(7):860-6
references: 16861916
references: Asian Pac J Cancer Prev. 2008 Apr-Jun;9(2):343-49
references: 18712988
references: J Urol. 2009 Sep;182(3):1178-85
references: 19625063
references: Mol Cell. 2000 Jul;6(1):173-82
references: 10949038
references: Ann N Y Acad Sci. 2002 Apr;959:341-54
references: 11976208
references: Biochem Biophys Res Commun. 2011 Apr 8;407(2):412-9
references: 21402055
references: J Biol Chem. 2002 Oct 4;277(40):37630-6
references: 12145284
references: Mol Cell Endocrinol. 2012 Mar 5;350(1):39-52
references: 22138414
references: Clin Exp Metastasis. 2006;23(5-6):279-89
references: 17086357
references: Cancer Res. 2008 Jul 1;68(13):5159-66
references: 18593915
references: Carcinogenesis. 2012 Jan;33(1):156-63
references: 22072621
references: Carcinogenesis. 2009 Jul;30(7):1202-8
references: 19406931