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You Haven't Heard the End of It: Telomere Loss May Link Human Aging with Cancer

Published online by Cambridge University Press:  29 November 2010

Jerry W. Shay
Affiliation:
The University of Texas Southwestern Medical Center at Dallas*
Harold Werbin
Affiliation:
The University of Texas Southwestern Medical Center at Dallas*
Woodring E. Wright
Affiliation:
The University of Texas Southwestern Medical Center at Dallas*

Résumé:

Des mécanismes moléculaires liant le cancer à la sénescence cellulaire sont présentement explorés. Les télomères (l'extrémité des chromosomes) raccourcissent à chaque division cellulaire et il a été proposé que ce raccourcissement soit l'horloge moléculaire qui déclenche le processus de la sénescence cellulaire. La re-expression de la télomérase, une enzyme qui aide à maintenir la longueur des télomères et à prévenir leur raccourcissement, est un événement fréquemment observé dans les cellules tumorales. Cette re-expression est probablement essentielle à la formation et à la croissance soutenue de la majorité des cancers.

Type
Articles
Copyright
Copyright © Canadian Association on Gerontology 1995

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References

1.Hastie, N.D., Dempster, M., Dunlop, M.G., Thompson, A.M., Green, D.K., Allshire, R.C.Telomere reduction in human colorectal carcinoma and with ageing. Nature. 1990, 346, 866868.CrossRefGoogle ScholarPubMed
2.Harley, C.B., Futcher, B.A., Greider, C.W.Telomeres shorten during ageing of human fibroblasts. Nature. 1990, 345, 458460.CrossRefGoogle ScholarPubMed
3.Harley, C.B.Telomere loss: mitotic clock or genetic time bomb? Mutation Res. 1991, 256, 271282.CrossRefGoogle ScholarPubMed
4.Harley, C.B., Vaziri, H., Counter, M.C., Allsopp, R.C.The telomere hypothesis of cellular aging. Exp Gerontology. 1992, 27, 375382.CrossRefGoogle ScholarPubMed
5.Vaziri, H., Dragowska, W., Allsopp, R.C., Thomas, T.E., Harley, C.B., Landsdorp, P.M.Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Nat'l Acad Sci USA. 1994, 91, 98579860.CrossRefGoogle ScholarPubMed
6.de Lange, T.Human telomeres are attached to the nuclear matrix. EMBO J. 1992, 11, 717724.CrossRefGoogle ScholarPubMed
7.Dawe, R.K., Sedat, J.W., Agard, D.A., Canade, W.Z.Meiotic chromosome pairing in maize is associated with a novel chromatin organization. Cell. 1994, 76, 901912.CrossRefGoogle ScholarPubMed
8.Gilson, E., LaRoche, T., Gasser, S.M.Telomeres and the functional architecture of the nucleus. Trends in Cell Biol. 1993, 3, 128134.CrossRefGoogle ScholarPubMed
9.Williamson, J.R.Commentary G-quartets in biology: reprise. Proc Nat'l Acad Sci USA. 1993, 90, 3124.CrossRefGoogle ScholarPubMed
10.Greider, C.W.Telomerase and telomere-length regulation: lessons from small eukaryotes to mammals. Cold Spring Harbor Quantit Biology. 1993, 43, 719723.CrossRefGoogle Scholar
11.Morin, G.B.The human telomere terminal transferase enzyme is a ribonucleo-protein that synthesizes TTAGGG repeats. Cell. 1989, 59, 521529.CrossRefGoogle Scholar
12.Moyzis, R.K, Buckingham, J.M., Cram, L.S., Dani, M., Daven, L.L., Jones, M.D., Meyne, J., Ratliff, R.L., Wu, J.-R.A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Nat'l Acad Sci USA. 1988, 85, 66226626.CrossRefGoogle ScholarPubMed
13.Cross, S.H., Allshire, R.C., McKay, S.J., McGill, N.I., Cooke, H.J.Cloning of human telomeres by complementation in yeast. Nature. 1989, 338, 771774.CrossRefGoogle ScholarPubMed
14.de Lange, T., Shiue, L., Myers, R.M., Cox, D.R., Naylor, S.L., Killery, A.M., Varmus, H., E., Structureand variability of human chromosome ends. Mol Cell Biol. 1993, 10, 518527.Google Scholar
15.Counter, C.M., Avillon, A.A., LeFeuvre, C.E., Stewart, N.G., Greider, C.W., Harley, C.B., Bacchetti, S.Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 1992, 11, 19211929.CrossRefGoogle ScholarPubMed
16.Blackburn, E.H.Telomeres: no end in sight. Cell. 1994, 77, 621623.CrossRefGoogle Scholar
17.Waga, S., Stillman, B.Anatomy of a DNA replication fork revealed by reconstitution of SV40 DNA replication in vitro. Nature. 1994, 369, 207212.CrossRefGoogle ScholarPubMed
18.Stukenberg, P.T., Turner, J., O'Donnell, M.An explanation for lagging strand replication: polymerase hopping among DNA sliding clamps. Cell. 1994, 78, 877887.CrossRefGoogle ScholarPubMed
19.Cross, S., Lindsey, J., Fantes, J., McKay, S., McGill, N., Cooke, H.The structure of a subterminal repeated sequence present on many chromosomes. Nucl Acids Res. 1990, 18, 66496657.CrossRefGoogle Scholar
20.Levy, M.Z., Allsopp, R.C., Futcher, A.B., Greider, C.W., Harley, C.B.Telomere endreplication problem and cell aging. J Mol Biol. 1992, 225, 951960.CrossRefGoogle ScholarPubMed
21.Harley, et al. (personal communication).Google Scholar
22.Shay, J.W., Wright, W.E., Brasiskyte, D., Van der Haegen, B.A.E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts. Oncogene. 1993, 8, 14071413.Google ScholarPubMed
23.Vaziri, H., Schachter, F., Uchida, I., Wei, L., Zhu, X., Effros, R., Cohen, D., Harley, C.B.Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet. 1993, 52, 661667.Google ScholarPubMed
24.Blackburn, E.H.Telomerases. Annu Rev Biochem. 1992, 61, 113129.CrossRefGoogle ScholarPubMed
25.Klingelhutz, A.J., Barber, S.A., Smith, P.P., Dyer, K., McDougall, J.K.Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells. Mol Cell Biol. 1994, 14, 961969.Google ScholarPubMed
26.Allsopp, R.C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E.V., Futcher, A.B., Greider, C.W., Harley, C.B.Telomere length predicts replicative capacity of human fibroblasts. Proc Nat'l Acad Sci USA. 1992, 89, 1011410118.CrossRefGoogle ScholarPubMed
27.Wright, W., Pereira-Smith, O., Shay, J.W.Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts. Mol Cell Biol. 1989, 9, 30883092.Google ScholarPubMed
28.Shay, J.W., Pereira-Smith, O., Wright, W.A role for both Rb and p53 in the regulation of human cellular senescence. Exp Cell Res. 1991, 196, 3339.CrossRefGoogle ScholarPubMed
29.Wright, W.E., Shay, J.W.Telomere positional effects and the regulation of cellular senescence. Trends Genet. 1991, 8, 193197.CrossRefGoogle Scholar
30.Wright, W.E., Shay, J.W.The two-stage mechanism controlling cellular senescence and immortalization. Exp Geront. 1992, 27, 383389.CrossRefGoogle ScholarPubMed
31.Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L.C., Coviello, G.M., Wright, W.W., Weinrich, S.L., Shay, J.W.Specific association of human telomerase activity with immortal cells and cancer. Science. 1994, 266, 20112015.CrossRefGoogle ScholarPubMed
32.Murnane, J.P., Sabatier, L., Marder, B.A., Morgan, W.F.Telomere dynamics in an immortal human cell line. EMBO J. 1994, 13, 49534962.CrossRefGoogle Scholar
33.Counter, C.M., Hirte, H.W., Bacchetti, S., Harley, C.B.Telomerase activity in human ovarian carcinoma. Proc Natl Acad Sci (U.S.A). 1994, 91, 29002904.CrossRefGoogle ScholarPubMed
34.Hiyama, E., Yokoyama, T., Hiyama, K., Yamakido, M., Santo, T., Kodama, T., Ichikawa, T., Matsuura, Y.Alteration of telomeric repeat length in adult and childhood solid neoplasia. Intern J Oncol. 1995, 6, 1316.Google Scholar
35.Schmitt, H., Blin, N., Zandl, H., Scherthan, H.Telomere length variation in normal and malignant human tissues. Genes, Chromosomes & Cancer. 1994, 11, 171177.Google ScholarPubMed
36.Hiyama, E., Hiyama, K., Yokoyama, T., Matsuura, Y., Piatyszek, M.A, Shay, J.W.Correlating telomerase activity levels with human neuroblastoma outcomes. Nature Medicine. 1995, 1, 249257.CrossRefGoogle ScholarPubMed
37.Hiyama, K., Hiyama, E., Ishioka, S., Yamakido, M., Inai, K., Gazdar, A.F., Piatyszek, M.A., Shay, J.W.Telomerase activity in small-cell and non-small-cell lung cancers. J Nat Cancer Inst. 1995, 87, 895902.CrossRefGoogle ScholarPubMed
38.Shay, J.W., Werbin, H., Wright, W.E.Telomere shortening may contribute to aging and cancer: a perspective. Mol Cell Differen. 1994, 2, 121.Google Scholar
39.Piatyszek, M.A., Kim, N.W., Weinrich, S.L, Hiyama, K, Hiyama, E., Wright, W.E., Shay, J.W.Detection of telomerase activity in human cells and tumors by a telomeric repeat amplification protocol (TRAP). Methods Cell Sci. 1995. In press.CrossRefGoogle Scholar
40.Lundblad, V., Szostak, J.W.A mutant with a defect in telomere elongation leads to senescence in yeast. Cell. 1989, 57, 633643.CrossRefGoogle ScholarPubMed
41.Lundblad, V., Blackburn, E.H.An alternative pathway for yeast telomerase maintenance rescues estl senescence. Cell. 1993, 73, 347360.CrossRefGoogle Scholar
42.Wang, S.-S., Zakian, V.A.Telomere-telomere recombination provides an express pathway for telomere acquisition. Nature. 1990, 345, 456458.CrossRefGoogle ScholarPubMed
43.Mason, J.M., Biessmann, H.The unusual telomeres of Drosophila. Trends in Genet. 1995, 11, 5862.CrossRefGoogle ScholarPubMed
44.Liu, Z., Frantz, J.D., Gilbert, W., Tye, B.-K.Identification and characterization of a nuclease activity specific for G4 tetrastranded DNA. Proc Nat'l Acad Sci USA. 1993, 90, 31573161.CrossRefGoogle ScholarPubMed
45.Harley, C.B.Telomeres and aging: fact, fancy, and the future. J NIH Res. 1995, 7, 6468.Google Scholar
46.Tommerup, H., Dousmanis, A., de Lange, T.Unusual chromatin in human telomeres. Mol Cell Biol. 1994, 14, 57775785.Google ScholarPubMed
47.Shay, J.W., Brasiskyte, D., Ouellette, M., Piatyszek, M.A., Werbin, H., Ying, Y., Wright, W.E. Analysis of telomerase and telomeres. In: Adolph, K.W. (ed.), Methods in Molecular Genetics, vol. 5 Gene and Chromosome Analysis, Part C. New York: Academic Press, 1994, 263280.Google Scholar
48.Prowse, K.R., Greider, C.W.Developmental and tissue specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci (USA). 1995, 92, 48184822.CrossRefGoogle ScholarPubMed
49.Wright, W.E., Shay, J.W.Time, telomeres, and tumours: Is cellular senescence more than an anti cancer mechanism. Trend in Cell Biol. 1995, 5, 293297.CrossRefGoogle Scholar
50.Lansdorf, P.M.Telomere length and proliferation potential of hematopoietic stem cells. J Cell Sci. 1995, 108, 16.CrossRefGoogle Scholar