Multiple pathways for the regulation of telomerase activity

S. E. Holt, W. E. Wright, J. W. Shay

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

The ends of vertebrate chromosomes are composed of large tracts of a repeated sequence, TTAGGG, which are known as telomeres. Normal somatic cells progressively lose telomeric repeats with each successive cell division due to incomplete replication. Immortal and cancer cells compensate for telomeric loss by expressing the enzyme telomerase, an RNA-dependent DNA polymerase that maintains telomere length. Telomerase activity has been detected in almost 90% of all human cancers. Telomerase activity is generally absent in normal somatic tissues but is detected in adult testes, activated lymphocytes, and lower levels are expressed in proliferative cells of renewal tissues. Telomerase activity is downregulated in cells that exit the cell cycle via either terminal differentiation or (reversible) quiescence. Inhibition of telomerase activity in tumour cells may provide an effective way to treat cancer by potentially reducing the recurrence of tumours due to occult micrometastases. An understanding of the pathways involved in telomerase regulation will be important for determining the most practical means of inhibiting its activity.

Original languageEnglish (US)
Pages (from-to)761-766
Number of pages6
JournalEuropean Journal of Cancer Part A
Volume33
Issue number5
DOIs
StatePublished - Apr 1 1997

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Keywords

  • differentiation
  • immortalisation
  • quiescence
  • senescence
  • stem cells
  • telomeres

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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