Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Methyl-CpG binding proteins and cancer: are MeCpGs more important than MBDs?

Oncogene volume 21, pages 5394–5399 (2002)Cite this article

There are two major steps in cancer. Firstly, somatic cells lose growth controls and become sporadically transformed. The cause of transformation might be one or several of a variety of different environmental or genetic factors. However at this first stage there is only a minor risk for poor clinical prognosis. These primary tumours can then undergo a second step in which previously benign tumours are said to become malignant by their ability to form secondary tumours called metastases. Clinical prognosis for patients with metastasizing tumours is not optimistic. The aim of this review is to consider the role, if any, of methyl-CpG binding proteins in both stages of tumour progression.

Cancer is predominantly a genetic disease. Inactivation of tumour suppressor genes through changes in DNA sequence is a well-documented phenomenon in tumour progression (Knudson, 1997). However the voices arguing that cancer can also be caused through transcriptional silencing by DNA methylation, making it also an epigenetic disease, have been growing stronger over the past decade (Jones and Laird, 1999). By far the majority of reports linking DNA methylation and cancer focus on the observation that inappropriate transcriptional silencing of tumour suppressor genes is often accompanied by abnormal DNA methylation patterns in the regulatory sequences of these genes (Costello et al., 2000; Jones and Laird, 1999). This abnormal methylation is usually found at CpG islands. CpG islands are short, C- and G-rich sequences associated with the 5′ ends of genes which, despite being rich in the methylatable sequence CpG, are normally never methylated irrespective of the transcriptional status of the associated gene (Bird, 1987). The observation that transcriptionally silent tumour suppressor genes are occasionally associated with abnormally methylated CpG islands in tumours begs the following question. Has inappropriate CpG island methylation caused the silencing of this gene (i.e. gene inactivation via epigenetic change), or has island methylation occurred subsequent to the gene being silenced by some other mechanism (i.e. gene inactivation via genetic change)?

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  • Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR, Petersen GM, Kinzler KW, Vogelstein B, de la Chapelle A . 1993 Science 260: 812–816

  • Amir RE, Van Den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY . 1999 Nat. Genet. 23: 185–188

  • Anastasiadis PZ, Reynolds AB . 2000 J. Cell Sci. 113: 1319–1334

  • Bader S, Walker M, Harrison D . 2000 Br. J. Cancer 83: 1646–1649

  • Bader S, Walker M, Hendrich B, Bird A, Bird C, Hooper M, Wyllie A . 1999 Oncogene 18: 8044–8047

  • Bellacosa A, Cicchillitti L, Schepis F, Riccio A, Yeung AT, Matsumoto Y, Golemis EA, Genuardi M, Neri G . 1999 Proc. Natl. Acad. Sci. USA 96: 3969–3974

  • Bird A . 2002 Genes Dev. 16: 6–21

  • Bird AP . 1987 Trends Genet. 3: 342–347

  • Bird AP, Wolffe AP . 1999 Cell 99: 451–454

  • Bulmer M . 1986 Mol. Biol. Evol. 3: 322–329

  • Buschhausen G, Wittig B, Graessmann M, Graessmann A . 1987 Proc. Natl. Acad. Sci. USA 84: 1177–1181

  • Chan MF, van Amerongen R, Nijjar T, Cuppen E, Jones PA, Laird PW . 2001 Mol. Cell. Biol. 21: 7587–7600

  • Chen RZ, Akbarian S, Tudor M, Jaenisch R . 2001 Nat. Genet. 27: 327–331

  • Cooper DN, Krawczak M . 1989 Hum. Genet. 83: 181–188

  • Cormier RT, Dove WF . 2000 Cancer Res. 60: 3965–3970

  • Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomaki P, Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Su Huang H, Petrelli NJ, Zhang X, O'Dorisio MS, Held WA, Cavenee WK, Plass C . 2000 Nat. Genet. 24: 132–138

  • Cross S, Meehan R, Nan X, Bird A . 1997 Nat. Genet. 13: 256–259

  • Daniel JM, Reynolds AB . 1999 Mol. Cell. Biol. 19: 3614–3623

  • Duncan BK, Miller JH . 1980 Nature 287: 560–561

  • Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB, Herman JG . 2000 Cancer Res. 60: 129–133

  • Foster SA, Wong DJ, Barrett MT, Galloway DA . 1998 Mol. Cell. Biol. 18: 1793–1801

  • Guy J, Hendrich B, Holmes M, Martin JE, Bird A . 2001 Nat. Genet. 27: 322–326

  • Hendrich B, Bird A . 1998 Mol. Cell. Biol. 18: 6538–6547

  • Hendrich B, Bird A . 2000 Curr. Top. Microbiol. Immunol. 249: 55–74

  • Hendrich B, Guy J, Ramsahoye B, Wilson VA, Bird A . 2001 Genes Dev. 15: 710–723

  • Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A . 1999 Nature 401: 301–304

  • Hollstein M, Rice K, Greenblatt MS, Soussi T, Fuchs R, Sorlie T, Hovig E, Smith-Sorensen B, Montesano R, Harris CC . 1994 Nucleic Acids Res. 22: 3551–3555

  • Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M . 1993 Nature 363: 558–561

  • Jones PA, Laird PW . 1999 Nature Genetics 21: 163–167

  • Jones PA, Rideout III WM, Shen JC, Spruck CH, Tsai YC . 1992 Bioessays 14: 33–36

  • Jones PL, Veenstra GJC, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP . 1998 Nat. Genetics 19: 187–191

  • Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day III RS, Johnson BE, Skolnick MH . 1994 Science 264: 436–440

  • Kanai Y, Ushijima S, Nakanishi Y, Hirohashi S . 1999 Biochem. Biophys. Res. Commun. 264: 962–966

  • Kass SU, Landsberger N, Wolffe AP . 1997 Curr. Biol. 7: 157–165

  • Kerr AM, Nomura Y, Armstrong D, Anvret M, Belichenko PV, Budden S, Cass H, Christodoulou J, Clarke A, Ellaway C, d'Esposito M, Francke U, Hulten M, Julu P, Leonard H, Naidu S, Schanen C, Webb T, Engerstrom IW, Yamashita Y, Segawa M . 2001 Brain Dev. 23: 208–211

  • Kerr AM, Stephenson JB . 1985 Br. Med. J. (Clin Res Ed) 291: 579–582

  • Knudson AG . 1997 Ann. NY Acad. Sci. 833: 58–67

  • Laird PW, Jackson-Grusby L, Fazeli A, Dickinson SL, Jung WE, Li E, Weinberg RA, Jaenisch R . 1995 Cell 81: 197–205

  • Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, Klein F, Bird A . 1992 Cell 69: 905–914

  • Lindahl T, Karran P, Wood RD . 1997 Curr. Opin. Genet. Dev. 7: 158–169

  • Magdinier F, Wolffe AP . 2001 Proc. Natl. Acad. Sci. USA 98: 4990–4995

  • Muller-Tidow C, Kugler K, Diederichs S, Klumpen S, Moller M, Vogt U, Metzger R, Schneider PM, Berdel WE, Serve H . 2001 Br. J. Cancer 85: 1168–1174

  • Nan X, Campoy F, Bird A . 1997 Cell 88: 471–481

  • Nan X, Meehan RR, Bird A . 1993 Nucleic Acids Res. 21: 4886–4892

  • Nan X, Ng H-H, Johnson CA, Laherty CD, Turner BM, Eisenmann RN, Bird A . 1998 Nature 393: 386–389

  • Nan X, Tate P, Li E, Bird A . 1996 Mol. Cell. Biol. 16: 414–421

  • Neddermann P, Gallinari P, Lettieri T, Schmid D, Truong O, Hsuan JJ, Wiebauer K, Jiricny J . 1996 J. Biol. Chem. 271: 12767–12774

  • Ng HH, Jeppesen P, Bird A . 2000 Mol. Cell. Biol. 20: 1394–1406

  • Nguyen CT, Gonzales FA, Jones PA . 2001 Nucleic Acids Res. 29: 4598–4606

  • Nuovo GJ, Plaia TW, Belinsky SA, Baylin SB, Herman JG . 1999 Proc. Natl. Acad. Sci. USA 96: 12754–12759

  • Petronzelli F, Riccio A, Markham GD, Seeholzer SH, Genuardi M, Karbowski M, Yeung AT, Matsumoto Y, Bellacosa A . 2000 J. Cell Physiol. 185: 473–480

  • Prokhortchouk A, Hendrich B, Jorgensen H, Ruzov A, Wilm M, Georgiev G, Bird A, Prokhortchouk E . 2001 Genes Dev. 15: 1613–1618

  • Riccio A, Aaltonen LA, Godwin AK, Loukola A, Percesepe A, Salovaara R, Masciullo V, Genuardi M, Paravatou-Petsotas M, Bassi DE, Ruggeri BA, Klein-Szanto AJ, Testa JR, Neri G, Bellacosa A . 1999 Nat. Genet. 23: 266–268

  • Robertson KD, Jones PA . 1998 Mol. Cell. Biol. 18: 6457–6473

  • Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S . 2001 Hepatology 33: 561–568

  • Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA, Dove WF . 1992 Science 256: 668–670

  • Sved J, Bird A . 1990 Proc. Natl. Acad. Sci. USA 87: 4692–4696

  • Thibodeau SN, Bren G, Schaid D . 1993 Science 260: 816–819

  • van Hengel J, Vanhoenacker P, Staes K, van Roy F . 1999 Proc. Natl. Acad. Sci. USA 96: 7980–7985

  • Wade PA . 2001 Oncogene 20: 3166–3173

  • Wiebauer K, Jiricny J . 1989 Nature 339: 234–236

Download references

Acknowledgements

We thank Adrian Bird and Owen Sansom for useful discussions and Catherine Millar and Susan Tweedie for critical reading of the manuscript. E Prokhortchouk is funded by the US Civilian Research and Development Foundation (CRDF), and B Hendrich is funded by the Wellcome Trust.

Author information

Authors and Affiliations

  1. Group of Transcriptional Control and Oncogenesis, Institute of Gene Biology, Vavilova 34/5, Moscow, 117334, Russian Federation

    Egor Prokhortchouk

  2. Centre for Genome Research, The University of Edinburgh, Roger Land Building, The King's Buildings, Edinburgh EH9 3JQ, Scotland, UK

    Brian Hendrich

Authors
  1. Egor Prokhortchouk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian Hendrich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Egor Prokhortchouk or Brian Hendrich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prokhortchouk, E., Hendrich, B. Methyl-CpG binding proteins and cancer: are MeCpGs more important than MBDs?. Oncogene 21, 5394–5399 (2002). https://doi.org/10.1038/sj.onc.1205631

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205631

Keywords

This article is cited by

Search

Advanced search

Quick links