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

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 p21^WAF1 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 p27^KIP1 were not altered by the induced expression of PKCη, the cyclin E associated Cdk2 kinase activity was in correlation with the p27^KIP1 bound to the cyclin E complex and not by p21^WAF1 binding. PKCη expression enhanced the removal of p27^KIP1 from this complex, and its re-association with the cyclin D/Cdk4 complex. Reduced binding of p27^KIP1 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 p21^WAF1 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.