Telomere shortening and apoptosis in telomerase-inhibited human tumor cells

X Zhang1, V Mar, W Zhou

  • 1Department of Cancer Biology, Amgen, Thousand Oaks, California 91320 USA.

Genes & Development
|September 29, 1999
PubMed

Insights

Telomerase inhibition in human tumor cells with short telomeres triggers cell death. This study shows telomerase is essential for cancer cell survival, suggesting a targeted therapy approach.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Telomerase activity strongly correlates with malignancy.
  • The impact of telomerase inhibition on human tumor cells remains largely unexamined.

Purpose of the Study:

  • To investigate the role of telomerase activity in human tumor and immortal cell proliferation.
  • To determine the outcome of inhibiting telomerase reverse transcriptase (TERT) function.

Main Methods:

  • Utilized inducible dominant-negative mutants of hTERT to inhibit telomerase activity in tumor cell lines.
  • Observed and analyzed cell division, mitosis, apoptosis, and telomere length in response to inhibition.

Main Results:

  • Inhibition of hTERT significantly reduced endogenous telomerase activity.
  • Cells with short telomeres underwent abnormal mitoses and massive apoptosis, leading to population loss.
  • Cell death was dependent on telomere length; cells with long telomeres survived but showed telomere shortening.

Conclusions:

  • Telomerase is essential for maintaining the viability of human tumor and immortal cells.
  • Telomere shortening and subsequent chromosomal damage trigger apoptosis upon telomerase inhibition.
  • Tumors with critically short telomeres represent a promising target for rapid eradication via telomerase inhibition.

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