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Regulation of the human telomerase reverse transcriptase gene

Abstract

Most somatic human cells lack telomerase activity because they do not express the telomerase reverse transcriptase (hTERT) gene. Conversely, most cancer cells express hTERT and are telomerase positive. For most tumors it is not clear whether hTERT expression is due to their origin from telomerase positive stem cells or to reactivation of the gene during tumorigenesis. Telomerase negative cells lack detectable cytoplasmic and nuclear hTERT transcripts; in telomerase positive cells 0.2 to 6 mRNA molecules/cell can be detected. This suggests that expression is regulated by changes in the rate of hTERT gene transcription. In tumor cell lines hTERT expression behaves like a recessive trait, indicating that lack of expression in normal cells is due to one or several repressors. Studies with monochromosomal hybrids indicate that several chromosomes may code for such repressors. A number of transcription factors, tumor suppressors, cell cycle inhibitors, cell fate determining molecules, hormone receptors and viral proteins have been implicated in the control of hTERT expression; but these studies have not yet provided a clear explanation for the tumor specific expression of the hTERT gene, and the cis-acting elements which are the targets of repression in normal cells still have to be identified.

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Acknowledgements

We thank Marc van de Wetering and Hans Clevers for providing us with RNA from colon carcinoma lines carrying tetracycline inducible dominant negative TCF variants, and allowing us to quote their unpublished results. One of us is much indebted to the medical and nursing staff of the Otorhinolaryngology unit of the Lausanne University Hospital and to Dr F Viani for their help in making it possible for him to get on with his contribution to the review. Work in the authors' laboratories is supported by the Swiss National Science Foundation, the Human Frontiers Science Program, the fifth framework program of the European Union (via the Bundesamt für Bildung und Wissenschaft, Bern), and Krebsforschung Schweiz and the Roche Research foundation.

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Correspondence to Markus Nabholz.

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Ducrest, AL., Szutorisz, H., Lingner, J. et al. Regulation of the human telomerase reverse transcriptase gene. Oncogene 21, 541–552 (2002). https://doi.org/10.1038/sj.onc.1205081

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Keywords

  • telomerase
  • hTERT
  • regulation
  • transcription
  • repression
  • tumor

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