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Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase

Oncogene volume 16, pages 12171222 (05 March 1998) | Download Citation

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Abstract

The expression of telomerase, the enzyme that synthesizes telomeric DNA de novo, is suppressed in normal somatic human cells but is reactivated during tumorigenesis. This reactivation appears to arrest the normal loss of telomeric DNA incurred as human cells divide. Since continual loss of telomeric DNA is predicted to eventually limit cell proliferation, activation of telomerase in cancer cells may represent an important step in the acquisition of the cell immortalization which occurs during tumor progression. The telomerase holoenzyme is composed of both RNA and protein subunits. In humans, mRNA expression of hTERT (hEST2), the candidate telomerase catalytic subunit gene, appears to parallel the levels of telomerase enzyme activity, suggesting that induction of hTERT is necessary and perhaps sufficient for expression of telomerase activity in tumor cells. To test this model directly, we ectopically expressed an epitope-tagged version of hTERT in telomerase-negative cells and show that telomerase activity was induced to levels comparable to those seen in immortal telomerase-positive cells and that the expressed hTERT protein was physically associated with the cellular telomerase activity. We conclude that synthesis of the hTERT telomerase subunit represents the rate-limiting determinant of telomerase activity in these cells and that this protein, once expressed, becomes part of the functional telomerase holoenzyme.

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Author notes

    • Christopher M Counter
    •  & Matthew Meyerson

    CM Counter and M Meyerson contributed equally to this work

Affiliations

  1. Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA

    • Christopher M Counter
    • , Matthew Meyerson
    • , Elinor Ng Eaton
    • , Stephanie Dickinson Caddle
    •  & Robert A Weinberg
  2. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

    • Matthew Meyerson
  3. Massachusetts General Hospital, Cancer Center, Charlestown, Massachusetts 02114, USA

    • Leif W Ellisen
    •  & Daniel A Haber

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Corresponding author

Correspondence to Robert A Weinberg.

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DOI

https://doi.org/10.1038/sj.onc.1201882

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