Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases

Cancer Lett. 2003 Dec 30;202(2):201-11. doi: 10.1016/s0304-3835(03)00517-2.


Human PRL-1, PRL-2, and PRL-3 tyrosine phosphatases induce the malignant transformation of epithelial cells. We tested the hypothesis that the oncogenic effects of PRL occur by increasing cellular proliferation. Cells stably transfected with PRL-1 or PRL-2 exhibited 2.7-3.3-fold increases over control cells in the rate of DNA synthesis and the proportion of cells in S-phase, and they progressed more rapidly from G1 into S. In addition, cells overexpressing either PRL-1 or PRL-2 exhibited enhanced cyclin-dependent kinase 2 (CDK2) activity and significantly lower p21(Cip1/Waf1) protein levels, and PRL-1 overexpressing cells had higher cyclin A protein levels than control cells. We conclude that PRL phosphatases increase cell proliferation by stimulating progression from G1 into S phase, and this process may be dependent on the down regulation of the cyclin dependent kinase inhibitor p21(Cip1/Waf1).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • CDC2-CDC28 Kinases / physiology
  • Cell Cycle / physiology*
  • Cell Division / physiology
  • Cells, Cultured
  • Cricetinae
  • Cyclin A / physiology
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / physiology*
  • Down-Regulation
  • Humans
  • Immunoblotting
  • Polymerase Chain Reaction
  • Precipitin Tests
  • Protein Tyrosine Phosphatases / physiology*
  • Transfection


  • CDKN1A protein, human
  • Cyclin A
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Protein Tyrosine Phosphatases