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:

Balancing instability: dual roles for telomerase and telomere dysfunction in tumorigenesis

Abstract

Telomere shortening and telomerase activation both occur in human tumors. Telomere shortening has been proposed to have two conflicting roles in tumorigenesis: tumor suppression and initiation of chromosomal instability. Similarly, while telomerase activation is suggested to be necessary for tumor growth, telomerase may help to stabilize genomic instability. Here we review what is known about these conflicting roles and propose a framework to understand the role of telomerase in cancer progression.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L, DePinho RA . 2000 Nature 406: 641–645

  • Bailey SM, Meyne J, Chen DJ, Kurimasa A, Li GC, Lehnert BE, Goodwin EH . 1999 Proc. Natl. Acad. Sci. USA 96: 14899–14904

  • Baumann P, Cech TR . 2000 Mol. Bio. Cell. 11: 3265–3275

  • Baumann P, Cech TR . 2001 Science 292: 1171–1175

  • Bianchi A, de Lange T . 1999 J. Biol. Chem. 274: 21223–21227

  • Blasco MA, Lee H-W, Hande PM, Samper E, Lansdorp PM, DePinho RA, Greider CW . 1997 Cell 91: 25–34

  • Bosco G, Haber JE . 1998 Genetics 150: 1037–1047

  • Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR . 1997 Nat. Med. 3: 1271–1274

  • Chadeneau C, Hay K, Hirte HW, Gallinger S, Bacchetti S . 1995 Cancer Res. 55: 2533–2536

  • Chin L, Artandi S, Shen Q, Tam S, Lee S-L, Gottlieb G, Greider CW, DePinho RA . 1999 Cell 97: 527–538

  • Conrad MN, Wright JH, Wolf AJ, Zakian VA . 1990 Cell 63: 739–750

  • Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S . 1992 EMBO J. 11: 1921–1929

  • de Lange T, Shiue L, Myers MR, Cox DR, Naylor SL, Killery AM, Varmus HE . 1990 Mol. Cell. Biol. 10: 518–527

  • DePinho RA . 2000 Nature 408: 248–254

  • Ducray C, Pommier JP, Martins L, Boussin FD, Sabatier L . 1999 Oncogene 18: 4211–4223

  • Ferguson DO, Sekiguchi JM, Chang S, Frank KM, Gao Y, DePinho RA, Alt FW . 2000 Proc. Natl. Acad. Sci. USA 97: 6630–6633

  • Ferreira MG, Cooper JP . 2001 Mol. Cell. 7: 55–63

  • Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C, van Es JH, Breukel C, Wiegant J, Giles RH, Clevers H . 2001 Nat. Cell. Biol. 3: 433–438

  • Gasser SM . 2000 Science 288: 1377–1379

  • Gray JT, Celander DW, Price CM, Cech TR . 1991 Cell 67: 807–814

  • Greenberg R, Chin L, Femino A, Lee K-H, Gottlieb G, Singer R, Greider CW, DePinho RA . 1999 Cell 97: 515–525

  • Greider CW . 2002 The Harvey Lectures Series 96 2000–2001 Vol. 96

  • Greider CW, Blackburn EH . 1989 Nature 337: 331–337

  • Griffith JD, Comeau L, Rosenfield S, Stansel R, Bianchi A, Moss H, de Lange T . 1999 Cell 97: 503–514

  • Guiducci C, Cerone MA, Bacchetti S . 2001 Oncogene 20: 714–725

  • Hackett JA, Feldser DM, Greider CW . 2001 Cell 106: 275–286

  • Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL, Knoll JH, Meyerson M, Weinberg RA . 1999 Nat. Med. 5: 1164–1170

  • Harley CB, Futcher AB, Greider CW . 1990 Nature 345: 458–460

  • Hemann MT, Strong MA, Hao L-Y, Greider CW . 2001 Cell 107: 67–77

  • Hicke B, Celander D, MacDonald G, Price C, Cech T . 1990 Proc. Natl. Acad. Sci. USA 87: 1481–1485

  • Hsu HL, Gilley D, Blackburn EH, Chen DJ . 1999 Proc. Natl. Acad. Sci. USA 96: 12454–12458

  • Hsu HL, Gilley D, Galande SA, Hande MP, Allen B, Kim SH, Li GC, Campisi J, Kohwi-Shigematsu T, Chen DJ . 2000 Genes Dev. 14: 2807–2812

  • Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Nathke IS . 2001 Nat. Cell. Biol. 3: 429–432

  • Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T . 1999 Science 283: 1321–1325

  • Killan A, Heller K, Kleinhofs A . 1998 Plant Molecular Biology 37: 621–628

  • Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PLC, Coviello GM, Wright WE, Weinrich SL, Shay JW . 1994 Science 266: 2011–2014

  • Kramer KM, Haber JE . 1993 Genes Dev. 7: 2345–2356

  • Lewis KL, Resnick MA . 2000 Mutat. Res. 451: 71–89

  • Lundblad V, Szostak JW . 1989 Cell 57: 633–643

  • Lustig AJ, Kurtz S, Shore D . 1990 Science 250: 549–552

  • Malkova A, Ivanov EL, Haber JE . 1996 Proc. Natl. Acad. Sci. USA 93: 7131–7136

  • McClintock B . 1941 Genetics 26: 234–282

  • McEachern MJ, Iyer S, Fulton TB, Blackburn EH . 2000 Proc. Natl. Acad. Sci. USA 97: 11409–11414

  • Muller HJ . 1938 Collecting Net. 13: 181–198

  • Myung K, Chen C, Kolodner RD . 2001 Nature 411: 1073–1076

  • Naito T, Matsuura A, Ishikawa F . 1998 Nat. Genet. 20: 203–206

  • Nakamura TM, Cooper JP, Cech TR . 1998 Science 282: 493–496

  • Peifer M, Polakis P . 2000 Science 287: 1606–1609

  • Rudolph KL, Chang S, Lee H-W, Blasco M, Gottlieb G, Greider CW, DePinho RA . 1999 Cell 96: 701–712

  • Rudolph KL, Millard M, Bosenberg MW, DePinho RA . 2001 Nat. Genet. 28: 155–159

  • Sandell LL, Zakian VA . 1993 Cell 75: 729–739

  • Sekiguchi J, Ferguson DO, Chen HT, Yang EM, Earle J, Frank K, Whitlow S, Gu Y, Xu Y, Nussenzweig A, Alt FW . 2001 Proc. Natl. Acad. Sci. USA 98: 3243–3248

  • Shay JW, Bacchetti S . 1997 Eur. J. Can. 33: 789–791

  • Shih IM, Zhou W, Goodman SN, Lengauer C, Kinzler KW, Vogelstein B . 2001 Cancer Res. 61: 818–822

  • Tang R, Cheng AJ, Wang JY, Wang TC . 1998 Cancer Res. 58: 4052–4054

  • Todaro GJ, Green H . 1963 J. Cell Biol. 17: 299–313

  • van Steensel B, Smogorzewska A, de Lange T . 1998 Cell 92: 401–413

  • Wang W, Skopp R, Scofield M, Price C . 1992 Nucleic Acids Res. 20: 6621–6629

  • Wright W, Shay JW . 1992 Trends Genet. 8: 193–197

  • Zakian VA . 1989 Annu. Rev. Genet. 23: 579–604

  • Zhang X, Mar V, Zhou W, Harrington L, Robinson MO . 1999 Genes Dev. 13: 2388–2399

  • Zhu XD, Kuster B, Mann M, Petrini JH, Lange T . 2000 Nat. Genet. 25: 347–352

Download references

Acknowledgements

We thank David Feldser, Mike Hemann, Doug Mason, Ling Qi, and Margaret Strong for critical reading of the manuscript. JA Hackett was supported by the Predoctoral Training Program in Human Genetics and Molecular Biology and a National Science Foundation Graduate Research Fellowship. This work was supported by NIH grant GM43080 to CW Greider.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carol W Greider.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hackett, J., Greider, C. Balancing instability: dual roles for telomerase and telomere dysfunction in tumorigenesis. Oncogene 21, 619–626 (2002). https://doi.org/10.1038/sj.onc.1205061

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205061

Keywords

This article is cited by

Search

Quick links