Medical Hypotheses
Volume 56, Issue 6 , Pages 630-637 , June 2001

Mechanisms for telomerase gene control in aging cells and tumorigenesis

Received 22 May 2000 ,Accepted 5 September 2000.

References 

    REFERENCES
  1. Greider CW. Telomere length regulation. Annu Rev Biochem. 1996;65:337–365
  2. Kirk KE, Harmon BP, Reichardt IK, Sedat JW, Blackburn EH. Block in anaphase chromosome separation caused by a telomerase template mutation. Science. 1997;275:1478–1481
  3. Zijlmans JM, Martens UM. Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3repeats. Proc Natl Acad Sci USA. 1997;94:7423–7428
  4. Makarov VL, Hirose Y, Langmore JP. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell. 1997;88:657–666
  5. Sedivy JM. Can ends justify the means? Telomeres and the mechanisms of replicative senescence and immortalization in mammalian cells. Proc Natl Acad Sci USA. 1998;95:9078–9081
  6. Holt SE, Shay JW. Role of telomerase in cellular proliferation and cancer. J Cell Physiol. 1999;180:10–18
  7. Greider CW. Telomerase activity, cell proliferation, and cancer. Proc Natl Acad Sci USA. 1998;95:90–92
  8. Morin GB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1998;59:521–529
  9. Nakamura TM, Morin GB, Chapman KB. Telomerase catalytic subunit homologs from fission yeast and humans. Science. 1997;277:955–959
  10. Harley CB, Futcher AB, Greider GW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–460
  11. Allsopp RC, Vaziri H, Patterson C. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA. 1992;89:10114–10118
  12. Campisi J. The biology of replicative senescence. Eur J Cancer. 1997;33:703–709
  13. deLange T, DePinho RA. Unlimited mileage from telomerase?. Science. 1999;283:947–949
  14. Bodnar AG, Quellette M, Frolkis M. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279:349–352
  15. Vaziri H, Benchimol S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicated life span. Current Biol. 1998;8:279–282
  16. Wang J, Xie Y, Allan S, Beach D, Hannon GJ. Myc activates telomerase. Genes and Devel. 1998;12:1744–1769
  17. Quellette MM, Aisner DL, Savre-Train I, Wright WE, Shay JW. Telomerase activity does not always imply telomere maintenance. Biochem Biophys Res Commun. 1999;254:795–803
  18. Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA, Klingelhutz AJ. Both Rb/p16ink4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature. 1998;396:84–88
  19. Morales CP, Holt SE, Quellette M. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nature Genet. 1999;21:115–118
  20. Feng J, Funk WD, Wang SS. The RNA component of human telomerase. Science. 1995;269:1236–1241
  21. Kondo S, Tanaka Y, Kondo Y. Antisense telomerase treatment: Induction of two distinct pathways, apoptosis and differentiation. FASEB J. 1998;12:801–811
  22. Hahn WC, Counter CM, Lundberg AS. Creation of human tumor cells with defined genetic elements. Nature. 1999;400:464–468
  23. Sharma HW, Sokoloski JA, Perez JR. Differentiation of immortal cells inhibits telomerase activity. Proc Natl Acad Sci USA. 1995;92:12343–12346
  24. Meyerson M, Counter CM, Eaton EN. hEST2, the putative human catalytic subunit gene, is up-regulated in tumor cells during immortalization. Cell. 1997;90:785–795
  25. Oh S, Song Y, Yim J, Kim TK. The Wilms tumor 1 tumor suppressor gene represses transcription of the human telomerase reverse transcriptase gene. J Biol Chem. 1999;274:37473–37478
  26. Xu D, Gruber A, Bjorkholm M, Peterson C. Suppression of telomerase reverse transcriptase (hTERT) expression in differentiated HL-60 cells: Regulatory mechanisms. Br J Cancer. 1999;80:1156–1161
  27. Ramakrishnan S, Eppenberger U, Mueller H, Shinkai Y, Narayanan R. Expression profile of the putative catalytic subunit of the telomerase gene. Cancer Res. 1999;58:622–625
  28. Nakayama J-I, Saito M, Nakamura H, Ishikawa F. TLP1: A gene encoding a protein component of mammalian telomerase is a member of WD repeats family. Cell. 1997;88:875–884
  29. Harrington L, McPhail T, Mar V. A mammalian telomerase-associated protein. Science. 1997;275:973–977
  30. Cong Y-S, Wen J, Bacchetti S. The human telomerase catalytic subunit hTERT: Organization of the gene and characterization of the promoter. Hum Mol Genet. 1999;8:137–142
  31. Horikawa I, Cable PL, Afshari C, Barrett JC. Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res. 1999;59:826–830
  32. Takakura M, Kyo S, Kanaya T. Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res. 1999;59:551–557
  33. Wick M, Zubov D, Hagen G. Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT). Gene. 1999;232:97–106
  34. Wu K-J, Grandori C, Amacker M. Direct activation of hTERT transcription by c-Myc. Nature Genet. 1999;21:220–224
  35. Wang J, Xie LY, Allan S, Beach D, Hannon GJ. Myc activates telomerase. Genes and Devel. 1998;12:1769–1774
  36. Siegfried Z, Eden S, Mendelsohn M, Fend X, Tsuberi B-Z, Cedar H. DNA methylation represses transcription in vivo.. Nature Genet. 1999;22:203–206
  37. Panning B, Jaenisch R. DNA methylation can activate Xist expression and silence X-linked genes. Cell. 1997;90:907–916
  38. Li E, Beard C, Jaenisch R. Role of DNA methylation in genomic imprinting. Nature. 1993;366:362–365
  39. Walsh CP, Chaillet JR, Bestor TH. Transcription of IAP endogenous retrovirus is constrained by cytosine methylation. Nature Genet. 1998;20:116–117
  40. Momparler RL, Bovenzi V. DNA methylation and cancer. J Cell Physiol. 2000;183:145–154
  41. Devereux TR, Horikawa I, Anna CH, Annab LA, Afshari CA, Barrett JC. DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res. 1999;59:6087–6090
  42. Dessain SK, Yu H, Reddel RR, Beijersbergen RL, Weinberg RA. Methylation of the human telomerase gene CpG island. Cancer Res. 2000;60:537–541
  43. Clark SJ, Harrison J, Frommer M. CpNpG methylation in mammalian cells. Nature Genet. 1995;10:20–27
  44. Christophe D, Pichon B. DNA methylation and gene activity: Toward the end of the debate?. Mol Cell Endocrin. 1994;100:155–158
  45. Byans M, Kass S, Seivwright C, Adams RLP. Vector methylation inhibits transcription from the SV40 early promoter. FEBS Lett. 1992;309:97–102
  46. Weih F, Nitsch D, Reik A, Schutz G, Becker PB. Analysis of CpG methylation and genomic footprinting at the tyrosine aminotransferase gene: DNA methylation alone is not sufficient to prevent protein binding in vivo.. EMBO J. 1991;10:2559–2567
  47. Kass SU, Goddard JP, Adams RLP. Inactive chromatin spreads from a focus of methylation. Mol Cell Biol. 1993;13:7372–7379
  48. Prendergast GC, Ziff EB. Methylation sensitive sequence-specific DNA binding by the c-Myc basic region. Science. 1991;251:186–189
  49. Zingg J-M, Jones PA. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis. 1997;18:869–882

PII: S0306-9877(00)91241-6

doi: 10.1054/mehy.2000.1241

Medical Hypotheses
Volume 56, Issue 6 , Pages 630-637 , June 2001

Article Tools