title: PKCeta enhances cell cycle progression, the expression of G1 cyclins and p21 in MCF-7 cells.
abstract: 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 PKCeta 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, PKCdelta, in MCF-7 cells had opposite effects and inhibited their growth. PKCeta 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 PKCeta 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 PKCeta, 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. PKCeta 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 PKCeta-expressing cells. Thus, PKCeta induces altered expression of several cell cycle functions, which may contribute to its ability to affect cell growth.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University, Beer Sheva 84105, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Fima
authors.forename: M
authors.initials: M
authors.lastname: Shtutman
authors.forename: P
authors.initials: P
authors.lastname: Libros
authors.forename: A
authors.initials: A
authors.lastname: Missel
authors.forename: G
authors.initials: G
authors.lastname: Shahaf
authors.forename: G
authors.initials: G
authors.lastname: Kahana
authors.forename: E
authors.initials: E
authors.lastname: Livneh
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division; D056741:Cyclin D; D019927:Cyclin E / Q000096:biosynthesis; D056746:Cyclin G; D056766:Cyclin G1; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis* / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D051745:Protein Kinase C-delta; D011518:Proto-Oncogene Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: C534702:CCNG1 protein, human; C493956:CDKN1A protein, human; D056741:Cyclin D; D019927:Cyclin E; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; D007527:Isoenzymes; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; C081975:protein kinase C eta; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases