PKCη enhances cell cycle progression, the expression of G1 cyclins and p21 in MCF-7 cells

Eyal Fima, Marat Shtutman, Pazit Libros, Adva Missel, Galit Shahaf, Galia Kahana, Etta Livneh

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Protein kinase C encodes a family of enzymes implicated in cellular differentiation, growth control and tumor promotion. However, not much is known with respect to the molecular mechanisms that link protein kinase C to cell cycle control. Here we report that the expression of PKCη in MCF-7 cells, under the control of a tetracycline-responsive inducible promoter, enhanced cell growth and affected the cell cycle at several points. The induced expression of another PKC isoform, PKCδ, in MCF-7 cells had opposite effects and inhibited their growth. PKCη expression activated cellular pathways in these cells that resulted in the increased expression of the G1 phase cyclins, cyclin D and cyclin E. Expression of the cyclin-dependent kinase inhibitor p21WAF1 was also specifically elevated in PKCη expressing cells, but its overall effects were not inhibitory. Although, the protein levels of the cyclin-dependent kinase inhibitor p27KIP1 were not altered by the induced expression of PKCη, the cyclin E associated Cdk2 kinase activity was in correlation with the p27KIP1 bound to the cyclin E complex and not by p21WAF1 binding. PKCη expression enhanced the removal of p27KIP1 from this complex, and its re-association with the cyclin D/Cdk4 complex. Reduced binding of p27KIP1 to the cyclin D/Cdk4 complex at early time points of the cell cycle also enhanced the activity of this complex, while at later time points the decrease in bound p21WAF1 correlated with its increased activity in PKCη-expressing cells. Thus, PKCη induces altered expression of several cell cycle functions, which may contribute to its ability to affect cell growth.

Original languageEnglish
Pages (from-to)6794-6804
Number of pages11
Issue number46
StatePublished - 11 Oct 2001


  • Cell cycle
  • Cyclin D
  • Cyclin E
  • MCF-7
  • PKCη
  • p21

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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