Role of telomerase in cellular proliferation and cancer

Shawn E. Holt, Jerry W. Shay

Research output: Contribution to journalReview articlepeer-review

209 Scopus citations

Abstract

Telomerase is a cellular reverse transcriptase that helps to provide genomic stability in highly proliferative normal, immortal, and tumor cells by maintaining the integrity of the chromosome ends, the telomeres. The activity of telomerase is associated with the majority of malignant human cancers. Telomerase or another mechanism for telomere maintenance is required for continuous tumor cell proliferation. Telomerase-positive cells that exit the cell cycle via quiescence downregulate telomerase through a transcriptional repression pathway. In the case of cell cycle exit via terminal differentiation, proteolysis of telomerase may also be involved. In response to mitogenic or growth factor signaling, telomerase-competent quiescent cells reenter the cell cycle and express telomerase activity independent of DNA synthesis. Under normal growth conditions, inhibition of telomerase activity in tumor-derived cells results in continued cell division coupled with telomere shortening, eventually followed by cellular senescence or death. Thus, repression of telomerase activity may be a novel adjuvant therapy for the treatment of human cancer and detection of telomerase activity may be important for cancer diagnostics.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalJournal of cellular physiology
Volume180
Issue number1
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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