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Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis

Nature Genetics volume 12, pages 200–204 (1996)Cite this article

Abstract

Telomeres consist of short repeated sequences that are synthesized by telomerase, a ribonucleo-protein DMA polymerase1–4. Telomerase activity is present in many tumours and not detected in many normal tissues5–7. Telomere shortening in human and mouse tissues and primary cell cultures may be due to the absence of telomerase activity8–11. To determine when telomerase is activated during tumour development and progression, we examined telomerase activity and expression of the recently cloned mouse telomerase RNA component (mTR)12 in two different transgenic mouse models of multi-stage tumorigenesis. These mouse models allow examination of many independent tumours from genetically identical individuals. These mice reproducibly develop pancreatic islet cell carcinoma13 and squamous cell carcinoma of the skin14. In both carcinoma types, we detected telomerase activity only in late-stage tumours; in contrast, we found mTR levels were upregulated in the early pre-neoplastic stages, and further increased during progression. Surprisingly, mTR levels did not parallel the amount of telomerase activity detected and a subset of tumours lacked telomerase activity and yet expressed telomerase RNA. Regulation of telomerase activity may therefore be separable from expression of its RNA component. These results clearly demonstrate telomerase is activated in late stages of tumour progression, and show for the first time that the initial up regulation of telomerase RNA is an early event, concurrent with the hyperproliferation elicited by viral oncogenes.

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Authors and Affiliations

  1. Cold Spring Harbor Laboratory, P.O. Box 100, 1 Bungtown Road, Cold Spring Harbor, New York, 11724, USA

    María A. Blasco & Carol W. Greider

  2. Department of Biochemistry and Biophysics, Hormone Research Institute, University of California, San Francisco, California, 94143-0534, USA

    Michael Rizen & Douglas Hanahan

Authors
  1. María A. Blasco
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  2. Michael Rizen
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  3. Carol W. Greider
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  4. Douglas Hanahan
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Blasco, M., Rizen, M., Greider, C. et al. Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis. Nat Genet 12, 200–204 (1996). https://doi.org/10.1038/ng0296-200

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