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Cited by 467

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas

Nakayama, Jun-ichi, Tahara, Hidetoshi, Tahara, Eiji, Saito, Motoki, Ito, Kaori, Nakamura, Hideo, Nakanishi, Toshio, Nakanishi, Eiichi, Ide, Toshinori, Ishikawa, Fuyuki·1998·Nature Genetics
DOI 10.1038/ng0198-65
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Abstract

Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis and extension of telomeric DNA (for review, see ref.1). This enzyme is highly active in most cancer cells, but is inactive in most somatic cells. This striking observation led to the suggestion that telomerase might be important for the continued growth or progression of cancer cells. However, little is known about the molecular mechanism of telomerase activation in cancer cells. Human telomerase reverse transcriptase (hTRT) has recently been identified as a putative human telomerase catalytic subunit. We transfected the gene encoding hTRT into telomerase-negative human normal fibroblast cells and demonstrated that expression of wild-type hTRT induces telomerase activity, whereas hTRT mutants containing mutations in regions conserved among other reverse transcriptases did not. Hepatocellular carcinoma (20 samples) and non-cancerous liver tissues (19 samples) were examined for telomerase activity and expression of hTRT, the human telomerase RNA component (hTR; encoded by TERC) and the human telomerase-associated protein (hTLP1; encoded by TEP1). A significant correlation between hTRT expression and telomerase activity was observed. These results indicate that the hTRT protein is the catalytic subunit of human telomerase, and that it plays a key role in the activation of telomerase in cancer cells.

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Citations

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Research works printed but not linked: 18

  1. Blackburn, E.H. Telomerase. Annu. Rev. Biochem. 61, 113–129 (1992) · DOI
  2. Harley, C.B. & Villeponteau, B. Telomeres and telomerase in aging and cancer Curr. Opin. Genet. Dev. 5, 249–255 (1995) · DOI
  3. Ishikawa, F. Telomere crisis, the driving force in cancer cell evolution. Biochem. Biophys. Res. Commun. 230, 1–6 (1997) · DOI
  4. Meyerson, M. et al. hE5T2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90, 785–795 (1997) · DOI · Paper page
  5. Nakamura, T.M. et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 277, 955–959 (1997) · DOI · Paper page
  6. Nakayama, J., Saito, M., Nakamura, H., Matsuura, A. & Ishikawa, f. TLP1: a gene encoding a protein component of mammalian telomerase is a novel member of WD repeats family. Cell 88, 875–884 (1997) · DOI
  7. Harrington, L et al.A mammalian telomerase-associated protein Science 275, 973–977 (1997) · DOI
  8. Lingner, J. et al. Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276, 561–567 (1997) · DOI · Paper page
  9. Counter, CM., Meyerson, M., Eaton, E.N. & Weinberg, R.A. The catalytic subunit of yeast telomerase. Proc. Natl. Acad. Sci. USA 94, 9202–9207 (1997) · DOI
  10. Graham, F.L., Smiley, J., Russell, W.C. & Nairn, R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. 36, 59–74 (1977) · DOI · Paper page
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  12. Jacobs, J.P., Jones, C.M. & Bailie, J.P. Nature 227, 168–170 (1970) · DOI
  13. Tatematsu, K. et al. A novel quantitative “stretch PCR assay”, that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias. Oncogene 13, 2265–2274 (1996)
  14. Steitz, T.A., Smerdon, S.J ., Jäger, J. & Joyce, C.M. A unified polymerase mechanism for nonhomologous DNA and RNA polymerases. Science 266, 2022–2025 (1994) · DOI · Paper page
  15. Nakashio, R. et al. Significance of telomerase activity in the diagnosis of small differentiated hepatocellular carcinoma. Int. J. Cancer 74, 141–147 (1997) · DOI
  16. Tahara, H. et al. Telomerase activity in human liver tissues: comparison between chronic liver disease and hepatocellular carcinomas. Cancer Res. 55, 2734–2736 (1995)
  17. Wright, W.E., Shay, J.W. & Piatyszek, M.A. Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity.Nucleic Acids Res. 23, 3794–3795 (1995) · DOI
  18. Eickbush, T.H. in The evolutionary biology of viruses (ed. Morse, S.S.) 121–157 (Raven Press, New York, 1994)

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Metadata

Authors
Nakayama, J.-I., Tahara, H., Tahara, E., Saito, M., Ito, K., Nakamura, H., Nakanishi, T., Nakanishi, E., Ide, T., & Ishikawa, F.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
1998-01
Volume
18
Issue
1
Pages
65-68
ISSN
  • 1061-4036
  • 1546-1718
DOI
10.1038/ng0198-65
Cited by
467
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. https://app.cochat.ai/papers/10.1038/ng0198-65
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Nakayama, J.-I., Tahara, H., Tahara, E., Saito, M., Ito, K., Nakamura, H., Nakanishi, T., Nakanishi, E., Ide, T., & Ishikawa, F. (1998). Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nature Genetics. https://doi.org/10.1038/ng0198-65