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Enforced expression of p14ARF induces p53-dependent cell cycle arrest but not apoptosis

Stuart Gallagher1, Richard F Kefford, Helen Rizos

  • 1Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, Australia.

Cell Cycle (Georgetown, Tex.)
|February 11, 2005
PubMed

Insights

The tumor suppressor p14ARF induces cell cycle arrest but not apoptosis. Loss of p14ARF may promote cancer cell resistance to apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The tumor suppressor p14ARF is induced by oncogenes and activates the p53 pathway to inhibit cell proliferation.
  • Loss of p14ARF is common in human cancers, potentially impairing the p53 response.
  • While p14ARF induces cell cycle arrest, its role in apoptosis is not well understood.

Purpose of the Study:

  • To investigate the effects of p14ARF on the survival and growth of human cells.
  • To determine if p14ARF induces apoptosis independently or in conjunction with other cellular stresses.

Main Methods:

  • Established inducible p14ARF expression in p53-intact and p53-deficient human cell lines, avoiding adenoviral vectors.
  • Assessed cell cycle arrest and apoptosis induction in response to p14ARF expression.
  • Investigated p14ARF's effect on apoptosis sensitivity in the presence of topoisomerase II and transcription inhibitors.

Main Results:

  • Inducible p14ARF expression caused cell cycle arrest in tumor cells with intact p53.
  • p14ARF did not induce apoptosis in primary fibroblasts or any tested tumor cell lines, regardless of p53 status.
  • p14ARF sensitized cells to apoptosis when combined with adriamycin (topoisomerase II inhibitor) or DRB (transcription inhibitor).

Conclusions:

  • p14ARF primarily induces cell cycle arrest, not direct apoptosis.
  • Loss of p14ARF may contribute to the development of apoptosis-resistant cancer cells.
  • p14ARF sensitizes cells to apoptosis under specific stress conditions, highlighting its role in tumor suppression.

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