Skip to main content

Advertisement

SpringerLink
Log in

Epigenetic regulation of mmp-9 gene expression

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Matrix metalloproteinase 9 (MMP-9) is one of the most studied enzymes in cancer. MMP-9 can cleave proteins of the extracellular matrix and a large number of receptors and growth factors. Accordingly, its expression must be tightly regulated to avoid excessive enzymatic activity, which is associated with disease progression. Although we know that epigenetic mechanisms play a central role in controlling mmp-9 gene expression, predicting how epigenetic drugs could be used to suppress mmp-9 gene expression is not trivial because epigenetic drugs also regulate the expression of key proteins that can tip the balance towards activation or suppression of MMP-9. Here, we review how our understanding of the biology and expression of MMP-9 could be exploited to augment clinical benefits, most notably in terms of the prevention and management of degenerative diseases and cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Zucker S, Cao J, Chen WT (2000) Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19:6642–6650. doi:10.1038/sj.onc.1204097

    Article  PubMed  CAS  Google Scholar 

  2. Kruger A, Soeltl R, Sopov I, Kopitz C, Arlt M, Magdolen V, Harbeck N, Gansbacher B, Schmitt M (2001) Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver metastasis. Cancer Res 61:1272–1275

    PubMed  CAS  Google Scholar 

  3. Arlt M, Kopitz C, Pennington C, Watson KL, Krell HW, Bode W, Gansbacher B, Khokha R, Edwards DR, Kruger A (2002) Increase in gelatinase-specificity of matrix metalloproteinase inhibitors correlates with antimetastatic efficacy in a T-cell lymphoma model. Cancer Res 62:5543–5550

    PubMed  CAS  Google Scholar 

  4. Kruger A, Kates RE, Edwards DR (2010) Avoiding spam in the proteolytic Internet: future strategies for anti-metastatic MMP inhibition. Biochim Biophys Acta 1803:95–102. doi:10.1016/j.bbamcr.2009.09.016

    Article  PubMed  CAS  Google Scholar 

  5. Gottschall PE, Deb S (1996) Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons. NeuroImmunoModulation 3:69–75

    Article  PubMed  CAS  Google Scholar 

  6. Yan C, Boyd DD (2007) Regulation of matrix metalloproteinase gene expression. J Cell Physiol 211:19–26. doi:10.1002/jcp.20948

    Article  PubMed  CAS  Google Scholar 

  7. Sato H, Seiki M (1993) Regulatory mechanism of 92-kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 8:395–405

    PubMed  CAS  Google Scholar 

  8. He C (1996) Molecular mechanism of transcriptional activation of human gelatinase B by proximal promoter. Cancer Lett 106:185–191 pii: 0304383596043182

    Article  PubMed  CAS  Google Scholar 

  9. Fini ME, Bartlett JD, Matsubara M, Rinehart WB, Mody MK, Girard MT, Rainville M (1994) The rabbit gene for 92-kDa matrix metalloproteinase. Role of AP1 and AP2 in cell type-specific transcription. J Biol Chem 269:28620–28628

    PubMed  CAS  Google Scholar 

  10. Gum R, Lengyel E, Juarez J, Chen JH, Sato H, Seiki M, Boyd D (1996) Stimulation of 92-kDa gelatinase B promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ets and AP-1 sequences. J Biol Chem 271:10672–10680

    Article  PubMed  CAS  Google Scholar 

  11. Shimajiri S, Arima N, Tanimoto A, Murata Y, Hamada T, Wang KY, Sasaguri Y (1999) Shortened microsatellite d(CA)21 sequence down-regulates promoter activity of matrix metalloproteinase 9 gene. FEBS Lett 455:70–74 pii: S0014-5793(99)00863-7

    Article  PubMed  CAS  Google Scholar 

  12. de Launoit Y, Baert JL, Chotteau-Lelievre A, Monte D, Coutte L, Mauen S, Firlej V, Degerny C, Verreman K (2006) The Ets transcription factors of the PEA3 group: transcriptional regulators in metastasis. Biochim Biophys Acta 1766:79–87. doi:10.1016/j.bbcan.2006.02.002

    PubMed  Google Scholar 

  13. Cowden Dahl KD, Zeineldin R, Hudson LG (2007) PEA3 is necessary for optimal epidermal growth factor receptor-stimulated matrix metalloproteinase expression and invasion of ovarian tumor cells. Mol Cancer Res 5:413–421. doi:10.1158/1541-7786.MCR-07-0019

    Article  PubMed  CAS  Google Scholar 

  14. Qin L, Liao L, Redmond A, Young L, Yuan Y, Chen H, O’Malley BW, Xu J (2008) The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression. Mol Cell Biol 28:5937–5950. doi:10.1128/MCB.00579-08

    Article  PubMed  CAS  Google Scholar 

  15. Farina AR, Tacconelli A, Vacca A, Maroder M, Gulino A, Mackay AR (1999) Transcriptional up-regulation of matrix metalloproteinase-9 expression during spontaneous epithelial to neuroblast phenotype conversion by SK-N-SH neuroblastoma cells, involved in enhanced invasivity, depends upon GT-box and nuclear factor kappaB elements. Cell Growth Differ 10:353–367

    PubMed  CAS  Google Scholar 

  16. Esteve PO, Chicoine E, Robledo O, Aoudjit F, Descoteaux A, Potworowski EF, St-Pierre Y (2002) Protein kinase C-zeta regulates transcription of the matrix metalloproteinase-9 gene induced by IL-1 and TNF-alpha in glioma cells via NF-kappa B. J Biol Chem 277:35150–35155. doi:10.1074/jbc.M108600200

    Article  PubMed  CAS  Google Scholar 

  17. Gum R, Wang H, Lengyel E, Juarez J, Boyd D (1997) Regulation of 92 kDa type IV collagenase expression by the jun aminoterminal kinase- and the extracellular signal-regulated kinase-dependent signaling cascades. Oncogene 14:1481–1493. doi:10.1038/sj.onc.1200973

    Article  PubMed  CAS  Google Scholar 

  18. Simon C, Goepfert H, Boyd D (1998) Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion. Cancer Res 58:1135–1139

    PubMed  CAS  Google Scholar 

  19. McCawley LJ, Li S, Wattenberg EV, Hudson LG (1999) Sustained activation of the mitogen-activated protein kinase pathway. A mechanism underlying receptor tyrosine kinase specificity for matrix metalloproteinase-9 induction and cell migration. J Biol Chem 274:4347–4353

    Article  PubMed  CAS  Google Scholar 

  20. Reddy KB, Krueger JS, Kondapaka SB, Diglio CA (1999) Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells. Int J Cancer 82:268–273. doi:10.1002/(SICI)1097-0215(19990719)82:2<268::AID-IJC18>3.0.CO;2-4

    Article  PubMed  CAS  Google Scholar 

  21. Karin M (1995) The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270:16483–16486

    PubMed  CAS  Google Scholar 

  22. Eberhardt W, Huwiler A, Beck KF, Walpen S, Pfeilschifter J (2000) Amplification of IL-1 beta-induced matrix metalloproteinase-9 expression by superoxide in rat glomerular mesangial cells is mediated by increased activities of NF-kappa B and activating protein-1 and involves activation of the mitogen-activated protein kinase pathways. J Immunol 165:5788–5797

    PubMed  CAS  Google Scholar 

  23. Bond M, Fabunmi RP, Baker AH, Newby AC (1998) Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B. FEBS Lett 435:29–34 pii: S0014-5793(98)01034-5

    Article  PubMed  CAS  Google Scholar 

  24. Sanceau J, Boyd DD, Seiki M, Bauvois B (2002) Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B. J Biol Chem 277:35766–35775. doi:10.1074/jbc.M202959200

    Article  PubMed  CAS  Google Scholar 

  25. St-Pierre Y, Couillard J, Van Themsche C (2004) Regulation of MMP-9 gene expression for the development of novel molecular targets against cancer and inflammatory diseases. Expert Opin Ther Targets 8:473–489. doi:10.1517/14728222.8.5.473

    Article  PubMed  CAS  Google Scholar 

  26. Chen PS, Shih YW, Huang HC, Cheng HW (2011) Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression. PLoS ONE 6:e20164. doi:10.1371/journal.pone.0020164

    Article  PubMed  CAS  Google Scholar 

  27. Ling H, Zhang Y, Ng KY, Chew EH (2011) Pachymic acid impairs breast cancer cell invasion by suppressing nuclear factor-kappaB-dependent matrix metalloproteinase-9 expression. Breast Cancer Res Treat 126:609–620. doi:10.1007/s10549-010-0929-5

    Article  PubMed  CAS  Google Scholar 

  28. Yeh CB, Hsieh MJ, Hsieh YH, Chien MH, Chiou HL, Yang SF (2012) Antimetastatic effects of norcantharidin on hepatocellular carcinoma by transcriptional inhibition of MMP-9 through modulation of NF-κB activity. PLoS ONE 7:e31055. doi:10.1371/journal.pone.0031055

    Article  PubMed  CAS  Google Scholar 

  29. Yan L, Borregaard N, Kjeldsen L, Moses MA (2001) The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL. J Biol Chem 276:37258–37265. doi:10.1074/jbc.M106089200

    Article  PubMed  CAS  Google Scholar 

  30. Lee JH, Welch DR (1997) Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1. Cancer Res 57:2384–2387

    PubMed  CAS  Google Scholar 

  31. Noda M, Takahashi C, Matsuzaki T, Kitayama H (2010) What we learn from transformation suppressor genes: lessons from RECK. Future Oncol 6:1105–1116. doi:10.2217/fon.10.80

    Article  PubMed  CAS  Google Scholar 

  32. Takahashi C, Sheng Z, Horan TP, Kitayama H, Maki M, Hitomi K, Kitaura Y, Takai S, Sasahara RM, Horimoto A, Ikawa Y, Ratzkin BJ, Arakawa T, Noda M (1998) Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc Natl Acad Sci USA 95:13221–13226

    Article  PubMed  CAS  Google Scholar 

  33. Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara RM, Nishimura S, Imamura Y, Kitayama H, Alexander DB, Ide C, Horan TP, Arakawa T, Yoshida H, Nishikawa S, Itoh Y, Seiki M, Itohara S, Takahashi C, Noda M (2001) The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107:789–800 pii: S0092-8674(01)00597-9

    Article  PubMed  CAS  Google Scholar 

  34. Takagi S, Simizu S, Osada H (2009) RECK negatively regulates matrix metalloproteinase-9 transcription. Cancer Res 69:1502–1508. doi:10.1158/0008-5472.CAN-08-2635

    Article  PubMed  CAS  Google Scholar 

  35. Esteve PO, Robledo O, Potworowski EF, St-Pierre Y (2002) Induced expression of MMP-9 in C6 glioma cells is inhibited by PDGF via a PI 3-kinase-dependent pathway. Biochem Biophys Res Commun 296:864–869 pii: S0006291X02020089

    Article  PubMed  CAS  Google Scholar 

  36. Das A, Fernandez-Zapico ME, Cao S, Yao J, Fiorucci S, Hebbel RP, Urrutia R, Shah VH (2006) Disruption of an SP2/KLF6 repression complex by SHP is required for farnesoid X receptor-induced endothelial cell migration. J Biol Chem 281:39105–39113. doi:10.1074/jbc.M607720200

    Article  PubMed  CAS  Google Scholar 

  37. Black AR, Black JD, Azizkhan-Clifford J (2001) Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 188:143–160. doi:10.1002/jcp.1111

    Article  PubMed  CAS  Google Scholar 

  38. Bouchard F, Belanger SD, Biron-Pain K, St-Pierre Y (2010) EGR-1 activation by EGF inhibits MMP-9 expression and lymphoma growth. Blood 116:759–766. doi:10.1182/blood-2009-12-257030

    Article  PubMed  CAS  Google Scholar 

  39. Ma J, Ren Z, Ma Y, Xu L, Zhao Y, Zheng C, Fang Y, Xue T, Sun B, Xiao W (2009) Targeted knockdown of EGR-1 inhibits IL-8 production and IL-8-mediated invasion of prostate cancer cells through suppressing EGR-1/NF-kappaB synergy. J Biol Chem 284:34600–34606. doi:10.1074/jbc.M109.016246

    Article  PubMed  CAS  Google Scholar 

  40. Waddington CH (2012) The epigenotype. 1942. Int J Epidemiol 41:10–13. doi:10.1093/ije/dyr184

    Article  PubMed  CAS  Google Scholar 

  41. Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92

    Article  PubMed  CAS  Google Scholar 

  42. Yoo CB, Jones PA (2006) Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 5:37–50. doi:10.1038/nrd1930

    Article  PubMed  CAS  Google Scholar 

  43. Mayo MW, Denlinger CE, Broad RM, Yeung F, Reilly ET, Shi Y, Jones DR (2003) Ineffectiveness of histone deacetylase inhibitors to induce apoptosis involves the transcriptional activation of NF-kappa B through the Akt pathway. J Biol Chem 278:18980–18989. doi:10.1074/jbc.M211695200

    Article  PubMed  CAS  Google Scholar 

  44. Ma Z, Shah RC, Chang MJ, Benveniste EN (2004) Coordination of cell signaling, chromatin remodeling, histone modifications, and regulator recruitment in human matrix metalloproteinase 9 gene transcription. Mol Cell Biol 24:5496–5509. doi:10.1128/MCB.24.12.5496-5509.2004

    Article  PubMed  CAS  Google Scholar 

  45. Houde M, de Bruyne G, Bracke M, Ingelman-Sundberg M, Skoglund G, Masure S, van Damme J, Opdenakker G (1993) Differential regulation of gelatinase B and tissue-type plasminogen activator expression in human Bowes melanoma cells. Int J Cancer 53:395–400

    Article  PubMed  CAS  Google Scholar 

  46. Juarez J, Clayman G, Nakajima M, Tanabe KK, Saya H, Nicolson GL, Boyd D (1993) Role and regulation of expression of 92-kDa type-IV collagenase (MMP-9) in 2 invasive squamous-cell-carcinoma cell lines of the oral cavity. Int J Cancer 55:10–18

    Article  PubMed  CAS  Google Scholar 

  47. Hanemaaijer R, Koolwijk P, le Clercq L, de Vree WJ, van Hinsbergh VW (1993) Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester. Biochem J 296(Pt 3):803–809

    PubMed  CAS  Google Scholar 

  48. Fini ME, Girard MT, Matsubara M, Bartlett JD (1995) Unique regulation of the matrix metalloproteinase, gelatinase B. Invest Ophthalmol Vis Sci 36:622–633

    PubMed  CAS  Google Scholar 

  49. Ma Z, Chang MJ, Shah RC, Benveniste EN (2005) Interferon-gamma-activated STAT-1alpha suppresses MMP-9 gene transcription by sequestration of the coactivators CBP/p300. J Leukoc Biol 78:515–523. doi:10.1189/jlb.0205112

    Article  PubMed  CAS  Google Scholar 

  50. Kaneko F, Saito H, Saito Y, Wakabayashi K, Nakamoto N, Tada S, Suzuki H, Tsunematsu S, Kumagai N, Ishii H (2004) Down-regulation of matrix-invasive potential of human liver cancer cells by type I interferon and a histone deacetylase inhibitor sodium butyrate. Int J Oncol 24:837–845

    PubMed  CAS  Google Scholar 

  51. Kuljaca S, Liu T, Tee AE, Haber M, Norris MD, Dwarte T, Marshall GM (2007) Enhancing the anti-angiogenic action of histone deacetylase inhibitors. Mol Cancer 6:68. doi:10.1186/1476-4598-6-68

    Article  PubMed  CAS  Google Scholar 

  52. Mitmaker EJ, Griff NJ, Grogan RH, Sarkar R, Kebebew E, Duh QY, Clark OH, Shen WT (2011) Modulation of matrix metalloproteinase activity in human thyroid cancer cell lines using demethylating agents and histone deacetylase inhibitors. Surgery 149:504–511. doi:10.1016/j.surg.2010.10.007

    Article  PubMed  Google Scholar 

  53. Lee KH, Choi EY, Kim MK, Kim KO, Jang BI, Kim SW, Song SK, Kim JR (2010) Inhibition of histone deacetylase activity down-regulates urokinase plasminogen activator and matrix metalloproteinase-9 expression in gastric cancer. Mol Cell Biochem 343:163–171. doi:10.1007/s11010-010-0510-x

    Article  PubMed  CAS  Google Scholar 

  54. Estella C, Herrer I, Atkinson SP, Quinonero A, Martinez S, Pellicer A, Simon C (2012) Inhibition of histone deacetylase activity in human endometrial stromal cells promotes extracellular matrix remodelling and limits embryo invasion. PLoS ONE 7:e30508. doi:10.1371/journal.pone.0030508

    Article  PubMed  CAS  Google Scholar 

  55. Reilly CM, Thomas M, Gogal R Jr, Olgun S, Santo A, Sodhi R, Samy ET, Peng SL, Gilkeson GS, Mishra N (2008) The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice. J Autoimmun 31:123–130. doi:10.1016/j.jaut.2008.04.020

    Article  PubMed  CAS  Google Scholar 

  56. Vinodhkumar R, Song YS, Ravikumar V, Ramakrishnan G, Devaki T (2007) Depsipeptide a histone deacetlyase inhibitor down regulates levels of matrix metalloproteinases 2 and 9 mRNA and protein expressions in lung cancer cells (A549). Chem Biol Interact 165:220–229. doi:10.1016/j.cbi.2006.12.012

    Article  PubMed  CAS  Google Scholar 

  57. http://www.clinicaltrials.gov/

  58. Lai MT, Yang CC, Lin TY, Tsai FJ, Chen WC (2008) Depsipeptide (FK228) inhibits growth of human prostate cancer cells. Urol Oncol 26:182–189. doi:10.1016/j.urolonc.2007.01.020

    Article  PubMed  CAS  Google Scholar 

  59. Sinn DI, Kim SJ, Chu K, Jung KH, Lee ST, Song EC, Kim JM, Park DK, Kun Lee S, Kim M, Roh JK (2007) Valproic acid-mediated neuroprotection in intracerebral hemorrhage via histone deacetylase inhibition and transcriptional activation. Neurobiol Dis 26:464–472. doi:10.1016/j.nbd.2007.02.006

    Article  PubMed  CAS  Google Scholar 

  60. Wang Z, Leng Y, Tsai LK, Leeds P, Chuang DM (2011) Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. J Cereb Blood Flow Metab 31:52–57. doi:10.1038/jcbfm.2010.195

    Article  PubMed  CAS  Google Scholar 

  61. Vinh A, Gaspari TA, Liu HB, Dousha LF, Widdop RE, Dear AE (2008) A novel histone deacetylase inhibitor reduces abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice. J Vasc Res 45:143–152. doi:10.1159/000110041

    Article  PubMed  CAS  Google Scholar 

  62. Liu HB, Voso MT, Gumiero D, Duong J, McKendrick JJ, Dear AE (2009) The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression. Int J Oncol 34:573–579

    PubMed  CAS  Google Scholar 

  63. Liu HB, Mayes PA, Perlmutter P, McKendrick JJ, Dear AE (2011) The anti-leukemic effect and molecular mechanisms of novel hydroxamate and benzamide histone deacetylase inhibitors with 5-aza-cytidine. Int J Oncol 38:1421–1425. doi:10.3892/ijo.2011.914

    PubMed  CAS  Google Scholar 

  64. Zhang ZY, Zhang Z, Schluesener HJ (2010) MS-275, an histone deacetylase inhibitor, reduces the inflammatory reaction in rat experimental autoimmune neuritis. Neuroscience 169:370–377. doi:10.1016/j.neuroscience.2010.04.074

    Article  PubMed  CAS  Google Scholar 

  65. Hsu MC, Chang HC, Hung WC (2006) HER-2/neu represses the metastasis suppressor RECK via ERK and Sp transcription factors to promote cell invasion. J Biol Chem 281:4718–4725. doi:10.1074/jbc.M510937200

    Article  PubMed  CAS  Google Scholar 

  66. Bosc DG, Goueli BS, Janknecht R (2001) HER2/Neu-mediated activation of the ETS transcription factor ER81 and its target gene MMP-1. Oncogene 20:6215–6224. doi:10.1038/sj.onc.1204820

    Article  PubMed  CAS  Google Scholar 

  67. Konecny G, Untch M, Arboleda J, Wilson C, Kahlert S, Boettcher B, Felber M, Beryt M, Lude S, Hepp H, Slamon D, Pegram M (2001) Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer. Clin Cancer Res 7:2448–2457

    PubMed  CAS  Google Scholar 

  68. Laughner E, Taghavi P, Chiles K, Mahon PC, Semenza GL (2001) HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol 21:3995–4004. doi:10.1128/MCB.21.12.3995-4004.2001

    Article  PubMed  CAS  Google Scholar 

  69. Howe LR, Subbaramaiah K, Patel J, Masferrer JL, Deora A, Hudis C, Thaler HT, Muller WJ, Du B, Brown AM, Dannenberg AJ (2002) Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res 62:5405–5407

    PubMed  CAS  Google Scholar 

  70. La Rocca G, Pucci-Minafra I, Marrazzo A, Taormina P, Minafra S (2004) Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera. Br J Cancer 90:1414–1421. doi:10.1038/sj.bjc.6601725

    Article  PubMed  CAS  Google Scholar 

  71. Jeon HW, Lee YM (2010) Inhibition of histone deacetylase attenuates hypoxia-induced migration and invasion of cancer cells via the restoration of RECK expression. Mol Cancer Ther 9:1361–1370. doi:10.1158/1535-7163.MCT-09-0717

    Article  PubMed  CAS  Google Scholar 

  72. Wanczyk M, Roszczenko K, Marcinkiewicz K, Bojarczuk K, Kowara M, Winiarska M (2011) HDACi–going through the mechanisms. Front Biosci 16:340–359 pii: 3691

    Article  CAS  Google Scholar 

  73. Marks PA (2007) Discovery and development of SAHA as an anticancer agent. Oncogene 26:1351–1356. doi:10.1038/sj.onc.1210204

    Article  PubMed  CAS  Google Scholar 

  74. Takada Y, Gillenwater A, Ichikawa H, Aggarwal BB (2006) Suberoylanilide hydroxamic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing nuclear factor-kappaB activation. J Biol Chem 281:5612–5622. doi:10.1074/jbc.M507213200

    Article  PubMed  CAS  Google Scholar 

  75. Choo QY, Ho PC, Tanaka Y, Lin HS (2010) Histone deacetylase inhibitors MS-275 and SAHA induced growth arrest and suppressed lipopolysaccharide-stimulated NF-kappaB p65 nuclear accumulation in human rheumatoid arthritis synovial fibroblastic E11 cells. Rheumatology (Oxford) 49:1447–1460. doi:10.1093/rheumatology/keq108

    Article  CAS  Google Scholar 

  76. Greer EL, Shi Y (2012) Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet 13:343–357. doi:10.1038/nrg3173

    Article  PubMed  CAS  Google Scholar 

  77. Ballestar E, Esteller M (2005) The epigenetic breakdown of cancer cells: from DNA methylation to histone modifications. Prog Mol Subcell Biol 38:169–181

    Article  PubMed  CAS  Google Scholar 

  78. Varier RA, Timmers HT (2011) Histone lysine methylation and demethylation pathways in cancer. Biochim Biophys Acta 1815:75–89. doi:10.1016/j.bbcan.2010.10.002

    PubMed  CAS  Google Scholar 

  79. Balemans MC, Huibers MM, Eikelenboom NW, Kuipers AJ, van Summeren RC, Pijpers MM, Tachibana M, Shinkai Y, van Bokhoven H, Van der Zee CE (2010) Reduced exploration, increased anxiety, and altered social behavior: autistic-like features of euchromatin histone methyltransferase 1 heterozygous knockout mice. Behav Brain Res 208:47–55. doi:10.1016/j.bbr.2009.11.008

    Article  PubMed  CAS  Google Scholar 

  80. Kleefstra T, van Zelst-Stams WA, Nillesen WM, Cormier-Daire V, Houge G, Foulds N, van Dooren M, Willemsen MH, Pfundt R, Turner A, Wilson M, McGaughran J, Rauch A, Zenker M, Adam MP, Innes M, Davies C, Lopez AG, Casalone R, Weber A, Brueton LA, Navarro AD, Bralo MP, Venselaar H, Stegmann SP, Yntema HG, van Bokhoven H, Brunner HG (2009) Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype. J Med Genet 46:598–606. doi:10.1136/jmg.2008.062950

    Article  PubMed  CAS  Google Scholar 

  81. Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, Ohashi H, Naritomi K, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Hasegawa T, Chinen Y, Tomita Ha HA, Kinoshita A, Mizuguchi T, Yoshiura Ki K, Ohta T, Kishino T, Fukushima Y, Niikawa N, Matsumoto N (2002) Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 30:365–366. doi:10.1038/ng863

    Article  PubMed  CAS  Google Scholar 

  82. Pollina EA, Brunet A (2011) Epigenetic regulation of aging stem cells. Oncogene 30:3105–3126. doi:10.1038/onc.2011.45

    Article  PubMed  CAS  Google Scholar 

  83. Cock-Rada AM, Medjkane S, Janski N, Yousfi N, Perichon M, Chaussepied M, Chluba J, Langsley G, Weitzman JB (2012) SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res 72:810–820. doi:10.1158/0008-5472.CAN-11-1052

    Article  PubMed  CAS  Google Scholar 

  84. Law JA, Jacobsen SE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11:204–220. doi:10.1038/nrg2719

    Article  PubMed  CAS  Google Scholar 

  85. Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9:2395–2402

    Article  PubMed  CAS  Google Scholar 

  86. Mohn F, Weber M, Rebhan M, Roloff TC, Richter J, Stadler MB, Bibel M, Schubeler D (2008) Lineage-specific Polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol Cell 30:755–766. doi:10.1016/j.molcel.2008.05.007

    Article  PubMed  CAS  Google Scholar 

  87. Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein BE, Nusbaum C, Jaffe DB, Gnirke A, Jaenisch R, Lander ES (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454:766–770. doi:10.1038/nature07107

    PubMed  CAS  Google Scholar 

  88. Sun Y, Kim H, Parker M, Stetler-Stevenson WG, Colburn NH (1996) Lack of suppression of tumor cell phenotype by overexpression of TIMP-3 in mouse JB6 tumor cells identification of a transfectant with increased tumorigenicity and invasiveness. Anticancer Res 16:1–7

    PubMed  Google Scholar 

  89. Chicoine E, Esteve PO, Robledo O, Van Themsche C, Potworowski EF, St-Pierre Y (2002) Evidence for the role of promoter methylation in the regulation of MMP-9 gene expression. Biochem Biophys Res Commun 297:765–772 pii: S0006291X02022830

    Article  PubMed  CAS  Google Scholar 

  90. Sato N, Maehara N, Su GH, Goggins M (2003) Effects of 5-aza-2′-deoxycytidine on matrix metalloproteinase expression and pancreatic cancer cell invasiveness. J Natl Cancer Inst 95:327–330

    Article  PubMed  CAS  Google Scholar 

  91. Gallagher WM, Bergin OE, Rafferty M, Kelly ZD, Nolan IM, Fox EJ, Culhane AC, McArdle L, Fraga MF, Hughes L, Currid CA, O’Mahony F, Byrne A, Murphy AA, Moss C, McDonnell S, Stallings RL, Plumb JA, Esteller M, Brown R, Dervan PA, Easty DJ (2005) Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies. Carcinogenesis 26:1856–1867. doi:10.1093/carcin/bgi152

    Article  PubMed  CAS  Google Scholar 

  92. Rhee I, Jair KW, Yen RW, Lengauer C, Herman JG, Kinzler KW, Vogelstein B, Baylin SB, Schuebel KE (2000) CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404:1003–1007. doi:10.1038/35010000

    Article  PubMed  CAS  Google Scholar 

  93. Couillard J, Demers M, Lavoie G, St-Pierre Y (2006) The role of DNA hypomethylation in the control of stromelysin gene expression. Biochem Biophys Res Commun 342:1233–1239. doi:10.1016/j.bbrc.2006.02.068

    Article  PubMed  CAS  Google Scholar 

  94. Chen KC, Wang YS, Hu CY, Chang WC, Liao YC, Dai CY, Juo SH (2011) OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J 25:1718–1728. doi:10.1096/fj.10-174904

    Article  PubMed  CAS  Google Scholar 

  95. Roach HI, Yamada N, Cheung KS, Tilley S, Clarke NM, Oreffo RO, Kokubun S, Bronner F (2005) Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum 52:3110–3124. doi:10.1002/art.21300

    Article  PubMed  CAS  Google Scholar 

  96. da Silva MA, Yamada N, Clarke NM, Roach HI (2009) Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J Orthop Res 27:593–601. doi:10.1002/jor.20799

    Article  PubMed  CAS  Google Scholar 

  97. Esteve PO, Chin HG, Smallwood A, Feehery GR, Gangisetty O, Karpf AR, Carey MF, Pradhan S (2006) Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication. Genes Dev 20:3089–3103. doi:10.1101/gad.1463706

    Article  PubMed  CAS  Google Scholar 

  98. Couillard J, Esteve PO, Pradhan S, St-Pierre Y (2011) 5-Aza-2′-deoxycytidine and interleukin-1 cooperate to regulate matrix metalloproteinase-3 gene expression. Int J Cancer 129:2083–2092. doi:10.1002/ijc.25865

    Article  PubMed  CAS  Google Scholar 

  99. Lavoie G, St-Pierre Y (2011) Phosphorylation of human DNMT1: implication of cyclin-dependent kinases. Biochem Biophys Res Commun 409:187–192. doi:10.1016/j.bbrc.2011.04.115

    Article  PubMed  CAS  Google Scholar 

  100. Eiseler T, Doppler H, Yan IK, Goodison S, Storz P (2009) Protein kinase D1 regulates matrix metalloproteinase expression and inhibits breast cancer cell invasion. Breast Cancer Res 11:R13. doi:10.1186/bcr2232

    Article  PubMed  CAS  Google Scholar 

  101. Storz P, Doppler H, Toker A (2005) Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. Mol Cell Biol 25:8520–8530. doi:10.1128/MCB.25.19.8520-8530.2005

    Article  PubMed  CAS  Google Scholar 

  102. Biswas MH, Du C, Zhang C, Straubhaar J, Languino LR, Balaji KC (2010) Protein kinase D1 inhibits cell proliferation through matrix metalloproteinase-2 and matrix metalloproteinase-9 secretion in prostate cancer. Cancer Res 70:2095–2104. doi:10.1158/0008-5472.CAN-09-4155

    Article  PubMed  CAS  Google Scholar 

  103. Ha CH, Wang W, Jhun BS, Wong C, Hausser A, Pfizenmaier K, McKinsey TA, Olson EN, Jin ZG (2008) Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J Biol Chem 283:14590–14599. doi:10.1074/jbc.M800264200

    Article  PubMed  CAS  Google Scholar 

  104. Sasahara RM, Brochado SM, Takahashi C, Oh J, Maria-Engler SS, Granjeiro JM, Noda M, Sogayar MC (2002) Transcriptional control of the RECK metastasis/angiogenesis suppressor gene. Cancer Detect Prev 26:435–443

    Article  PubMed  CAS  Google Scholar 

  105. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835–840. doi:10.1038/nature09267

    Article  PubMed  CAS  Google Scholar 

  106. McDermott AM, Heneghan HM, Miller N, Kerin MJ (2011) The therapeutic potential of microRNAs: disease modulators and drug targets. Pharm Res 28:3016–3029. doi:10.1007/s11095-011-0550-2

    Article  PubMed  CAS  Google Scholar 

  107. Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D (2008) Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 58:1001–1009. doi:10.1002/art.23386

    Article  PubMed  Google Scholar 

  108. Li X, Gibson G, Kim JS, Kroin J, Xu S, van Wijnen AJ, Im HJ (2011) MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis. Gene 480:34–41. doi:10.1016/j.gene.2011.03.003

    Article  PubMed  CAS  Google Scholar 

  109. Yamasaki K, Nakasa T, Miyaki S, Ishikawa M, Deie M, Adachi N, Yasunaga Y, Asahara H, Ochi M (2009) Expression of MicroRNA-146a in osteoarthritis cartilage. Arthritis Rheum 60:1035–1041. doi:10.1002/art.24404

    Article  PubMed  CAS  Google Scholar 

  110. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486. doi:10.1073/pnas.0605298103

    Article  PubMed  CAS  Google Scholar 

  111. Akhtar N, Rasheed Z, Ramamurthy S, Anbazhagan AN, Voss FR, Haqqi TM (2010) MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes. Arthritis Rheum 62:1361–1371. doi:10.1002/art.27329

    Article  PubMed  CAS  Google Scholar 

  112. Liang Z, Li Y, Huang K, Wagar N, Shim H (2011) Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN. Pharm Res 28:3091–3100. doi:10.1007/s11095-011-0570-y

    Article  PubMed  CAS  Google Scholar 

  113. Tardif G, Hum D, Pelletier JP, Duval N, Martel-Pelletier J (2009) Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC Musculoskelet Disord 10:148. doi:10.1186/1471-2474-10-148

    Article  PubMed  CAS  Google Scholar 

  114. Ucar A, Vafaizadeh V, Jarry H, Fiedler J, Klemmt PA, Thum T, Groner B, Chowdhury K (2010) miR-212 and miR-132 are required for epithelial stromal interactions necessary for mouse mammary gland development. Nat Genet 42:1101–1108. doi:10.1038/ng.709

    Article  PubMed  CAS  Google Scholar 

  115. Mayor-Lynn K, Toloubeydokhti T, Cruz AC, Chegini N (2011) Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod Sci 18:46–56. doi:10.1177/1933719110374115

    Article  PubMed  CAS  Google Scholar 

  116. Yan W, Zhang W, Sun L, Liu Y, You G, Wang Y, Kang C, You Y, Jiang T (2011) Identification of MMP-9-specific microRNA expression profile as potential targets of anti-invasion therapy in glioblastoma multiforme. Brain Res 1411:108–115. doi:10.1016/j.brainres.2011.07.002

    PubMed  CAS  Google Scholar 

  117. Liu P, Wilson MJ (2012) miR-520c and miR-373 upregulate MMP9 expression by targeting mTOR and SIRT1, and activate the Ras/Raf/MEK/Erk signaling pathway and NF-kappaB factor in human fibrosarcoma cells. J Cell Physiol 227:867–876. doi:10.1002/jcp.22993

    Article  PubMed  CAS  Google Scholar 

  118. Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS, Krichevsky AM (2008) MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol 28:5369–5380. doi:10.1128/MCB.00479-08

    Article  PubMed  CAS  Google Scholar 

  119. Song L, Huang Q, Chen K, Liu L, Lin C, Dai T, Yu C, Wu Z, Li J (2010) miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-beta. Biochem Biophys Res Commun 402:135–140. doi:10.1016/j.bbrc.2010.10.003

    Article  PubMed  CAS  Google Scholar 

  120. Lopez-Serra P, Esteller M (2012) DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene 31:1609–1622. doi:10.1038/onc.2011.354

    Article  PubMed  CAS  Google Scholar 

  121. Stanczyk J, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley CD, Tak PP, Gay S, Kyburz D (2011) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis Rheum 63:373–381. doi:10.1002/art.30115

    Article  PubMed  Google Scholar 

  122. Roy S, Khanna S, Hussain SR, Biswas S, Azad A, Rink C, Gnyawali S, Shilo S, Nuovo GJ, Sen CK (2009) MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc Res 82:21–29. doi:10.1093/cvr/cvp015

    Article  PubMed  CAS  Google Scholar 

  123. Liu H, Cao YD, Ye WX, Sun YY (2010) Effect of microRNA-206 on cytoskeleton remodelling by downregulating Cdc42 in MDA-MB-231 cells. Tumori 96:751–755

    PubMed  CAS  Google Scholar 

  124. Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, Leon LG, Pollina LE, Groen A, Falcone A, Danesi R, Campani D, Verheul HM, Boggi U (2010) MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res 70:4528–4538. doi:10.1158/0008-5472.CAN-09-4467

    Article  PubMed  CAS  Google Scholar 

  125. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033. doi:10.1158/0008-5472.CAN-05-0137

    Article  PubMed  CAS  Google Scholar 

  126. Reis ST, Pontes-Junior J, Antunesnes AA, Dall Oglio MF, Dip N, Passerotti CC, Rossini GA, Morais DR, Nesrallah AJ, Piantino C, Srougi M, Leite KR (2012) miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer. BMC Urol 12:14. doi:10.1186/1471-2490-12-14

    Article  PubMed  CAS  Google Scholar 

  127. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103:2257–2261. doi:10.1073/pnas.0510565103

    Article  PubMed  CAS  Google Scholar 

  128. Silverman LR, Mufti GJ (2005) Methylation inhibitor therapy in the treatment of myelodysplastic syndrome. Nat Clin Pract Oncol 2(Suppl 1):S12–23. doi:10.1038/ncponc0347

    Article  PubMed  CAS  Google Scholar 

  129. Issa JP, Kantarjian HM, Kirkpatrick P (2005) Azacitidine. Nat Rev Drug Discov 4:275–276. doi:10.1038/nrd1698

    Article  PubMed  CAS  Google Scholar 

  130. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10:223–232. doi:10.1016/S1470-2045(09)70003-8

    Article  PubMed  CAS  Google Scholar 

  131. Garg P, Sarma D, Jeppsson S, Patel NR, Gewirtz AT, Merlin D, Sitaraman SV (2010) Matrix metalloproteinase-9 functions as a tumor suppressor in colitis-associated cancer. Cancer Res 70:792–801. doi:10.1158/0008-5472.CAN-09-3166

    Article  PubMed  CAS  Google Scholar 

  132. Garg P, Ravi A, Patel NR, Roman J, Gewirtz AT, Merlin D, Sitaraman SV (2007) Matrix metalloproteinase-9 regulates MUC-2 expression through its effect on goblet cell differentiation. Gastroenterology 132:1877–1889. doi:10.1053/j.gastro.2007.02.048

    Article  PubMed  CAS  Google Scholar 

  133. Overall CM, Dean RA (2006) Degradomics: systems biology of the protease web. Pleiotropic roles of MMPs in cancer. Cancer Metastasis Rev 25:69–75. doi:10.1007/s10555-006-7890-0

    Article  PubMed  Google Scholar 

  134. Fanjul-Fernandez M, Folgueras AR, Cabrera S, Lopez-Otin C (2010) Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models. Biochim Biophys Acta 1803:3–19. doi:10.1016/j.bbamcr.2009.07.004

    Article  PubMed  CAS  Google Scholar 

  135. Emenaker NJ, Basson MD (1998) Short chain fatty acids inhibit human (SW1116) colon cancer cell invasion by reducing urokinase plasminogen activator activity and stimulating TIMP-1 and TIMP-2 activities, rather than via MMP modulation. J Surg Res 76:41–46. doi:10.1006/jsre.1998.5279

    Article  PubMed  CAS  Google Scholar 

  136. Zeng H, Briske-Anderson M (2005) Prolonged butyrate treatment inhibits the migration and invasion potential of HT1080 tumor cells. J Nutr 135:291–295 pii: 135/2/291

    PubMed  CAS  Google Scholar 

  137. Lee JC, Maa MC, Yu HS, Wang JH, Yen CK, Wang ST, Chen YJ, Liu Y, Jin YT, Leu TH (2005) Butyrate regulates the expression of c-Src and focal adhesion kinase and inhibits cell invasion of human colon cancer cells. Mol Carcinog 43:207–214. doi:10.1002/mc.20117

    Article  PubMed  CAS  Google Scholar 

  138. Rodriguez-Salvador J, Armas-Pineda C, Perezpena-Diazconti M, Chico-Ponce de Leon F, Sosa-Sainz G, Lezama P, Recillas-Targa F, Arenas-Huertero F (2005) Effect of sodium butyrate on pro-matrix metalloproteinase-9 and -2 differential secretion in pediatric tumors and cell lines. J Exp Clin Cancer Res 24:463–473

    PubMed  CAS  Google Scholar 

  139. Chen Y, Tsai YH, Tseng SH (2012) Valproic acid affected the survival and invasiveness of human glioma cells through diverse mechanisms. J Neurooncol. doi:10.1007/s11060-012-0871-y

    Google Scholar 

  140. Klisovic DD, Klisovic MI, Effron D, Liu S, Marcucci G, Katz SE (2005) Depsipeptide inhibits migration of primary and metastatic uveal melanoma cell lines in vitro: a potential strategy for uveal melanoma. Melanoma Res 15:147–153 pii: 00008390-200506000-00002

    Article  PubMed  CAS  Google Scholar 

  141. Sun Y, Hegamyer G, Kim H, Sithanandam K, Li H, Watts R, Colburn NH (1995) Molecular cloning of mouse tissue inhibitor of metalloproteinases-3 and its promoter. Specific lack of expression in neoplastic JB6 cells may reflect altered gene methylation. J Biol Chem 270:19312–19319

    Article  PubMed  CAS  Google Scholar 

  142. Xu F, Carlos T, Li M, Sanchez-Sweatman O, Khokha R, Gorelik E (1998) Inhibition of VLA-4 and up-regulation of TIMP-1 expression in B16BL6 melanoma cells transfected with MHC class I genes. Clin Exp Metastasis 16:358–370

    Article  PubMed  CAS  Google Scholar 

  143. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB (1999) Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 21:103–107. doi:10.1038/5047

    Article  PubMed  CAS  Google Scholar 

  144. Pennie WD, Hegamyer GA, Young MR, Colburn NH (1999) Specific methylation events contribute to the transcriptional repression of the mouse tissue inhibitor of metalloproteinases-3 gene in neoplastic cells. Cell Growth Differ 10:279–286

    PubMed  CAS  Google Scholar 

  145. Huang X, Orucevic A, Li M, Gorelik E (2000) Nitric oxide (NO), methylation and TIMP-1 expression in BL6 melanoma cells transfected with MHC class I genes. Clin Exp Metastasis 18:329–335

    Article  PubMed  CAS  Google Scholar 

  146. Ivanova T, Vinokurova S, Petrenko A, Eshilev E, Solovyova N, Kisseljov F, Kisseljova N (2004) Frequent hypermethylation of 5′ flanking region of TIMP-2 gene in cervical cancer. Int J Cancer 108:882–886. doi:10.1002/ijc.11652

    Article  PubMed  CAS  Google Scholar 

  147. Bachman KE, Herman JG, Corn PG, Merlo A, Costello JF, Cavenee WK, Baylin SB, Graff JR (1999) Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res 59:798–802

    PubMed  CAS  Google Scholar 

  148. MacDougall JR, Bani MR, Lin Y, Muschel RJ, Kerbel RS (1999) ‘Proteolytic switching’: opposite patterns of regulation of gelatinase B and its inhibitor TIMP-1 during human melanoma progression and consequences of gelatinase B overexpression. Br J Cancer 80:504–512. doi:10.1038/sj.bjc.6690385

    Article  PubMed  CAS  Google Scholar 

  149. Gagnon J, Shaker S, Primeau M, Hurtubise A, Momparler RL (2003) Interaction of 5-aza-2′-deoxycytidine and depsipeptide on antineoplastic activity and activation of 14–3-3sigma, E-cadherin and tissue inhibitor of metalloproteinase 3 expression in human breast carcinoma cells. Anticancer Drugs 14:193–202. doi:10.1097/01.cad.0000060628.27490.28

    Article  PubMed  CAS  Google Scholar 

  150. Yuan BZ, Jefferson AM, Popescu NC, Reynolds SH (2004) Aberrant gene expression in human non small cell lung carcinoma cells exposed to demethylating agent 5-aza-2′-deoxycytidine. Neoplasia 6:412–419. doi:10.1593/neo.03490

    Article  PubMed  CAS  Google Scholar 

  151. Feng H, Cheung AN, Xue WC, Wang Y, Wang X, Fu S, Wang Q, Ngan HY, Tsao SW (2004) Down-regulation and promoter methylation of tissue inhibitor of metalloproteinase 3 in choriocarcinoma. Gynecol Oncol 94:375–382. doi:10.1016/j.ygyno.2004.04.019

    Article  PubMed  CAS  Google Scholar 

  152. Galm O, Suzuki H, Akiyama Y, Esteller M, Brock MV, Osieka R, Baylin SB, Herman JG (2005) Inactivation of the tissue inhibitor of metalloproteinases-2 gene by promoter hypermethylation in lymphoid malignancies. Oncogene 24:4799–4805. doi:10.1038/sj.onc.1208599

    Article  PubMed  CAS  Google Scholar 

  153. Pulukuri SM, Patibandla S, Patel J, Estes N, Rao JS (2007) Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors. Oncogene 26:5229–5237. doi:10.1038/sj.onc.1210329

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare no commercial or financial relationships that could be construed as a potential conflict of interest.

Author information

Authors and Affiliations

  1. INRS-Institut Armand-Frappier, 531 Boul. Des Prairies, Laval, QC, H7V 1B7, Canada

    Marilyne Labrie & Yves St-Pierre

Authors
  1. Marilyne Labrie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yves St-Pierre
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yves St-Pierre.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Labrie, M., St-Pierre, Y. Epigenetic regulation of mmp-9 gene expression. Cell. Mol. Life Sci. 70, 3109–3124 (2013). https://doi.org/10.1007/s00018-012-1214-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-012-1214-z

Keywords

Search

Navigation