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The p21 cyclin-dependent kinase inhibitor suppresses tumorigenicity in vivo

Z Y Yang1, N D Perkins, T Ohno

  • 1Howard Hughes Medical Institute, University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor 48109-0650, USA.

Nature Medicine
|October 1, 1995
PubMed

Insights

The p21 gene inhibits malignant cell growth and causes differentiation, not apoptosis. Gene transfer of p21 offers a novel approach to halt cancer progression by inducing terminal cell differentiation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The p21 gene encodes a cyclin-dependent kinase inhibitor.
  • Its role as a tumor suppressor in vivo remains unestablished.
  • p21 influences cell-cycle progression.

Purpose of the Study:

  • To investigate the in vivo tumor suppressor potential of the p21 gene.
  • To determine the effects of p21 expression on malignant cell growth and differentiation.

Main Methods:

  • Expression of p21 in malignant cells in vitro and in vivo.
  • Utilized adenoviral vectors for gene transfer of p21.
  • Monitored cell-cycle progression, morphology, differentiation, and apoptosis.

Main Results:

  • p21 expression inhibited malignant cell growth both in vitro and in vivo.
  • Accumulation of cells in the G0/G1 phase was observed.
  • Altered cell morphology and induced cell differentiation occurred, but apoptosis was not triggered.
  • Adenoviral delivery of p21 suppressed existing tumor growth.

Conclusions:

  • p21 functions as a tumor suppressor in vivo.
  • Gene transfer of p21 represents a potential molecular genetic strategy for cancer therapy.
  • p21 may irreversibly commit malignant cells to terminal differentiation, arresting cancer growth.

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