title: GH3B6 pituitary tumor cell proliferation is mediated by PKCalpha and PKCepsilon via ERK 1/2-dependent pathway.
abstract: BACKGROUND
  In this report, we explored the role of PKCalpha and PKCe as mediators of phorbol 12-myristate13-acetate (PMA)-induced proliferation in pituitary tumor GH3B6 cells, and determined if the ERK1/2 and Akt pathways were activated.
  
  
  METHODS
  The GH3B6 cell proliferation was estimated by BrdU incorporation and the cell cycle progression by flow cytometric cell cycle analysis. We determined the expression of PKCalpha and PKCe in membrane and cytosolic fractions by western blotting. The subcellular redistribution of both PKC isozymes was analyzed by confocal microscopy.
  
  
  RESULTS
  Incubation with PMA for 15 min stimulated PKCalpha and PKCe activation, which was correlated with the phosphorylation of ERK1/2 but not Akt. The activation of both these PKC isozymes was closely associated with the stimulation of proliferation and the cell cycle progression induced by PMA in GH3B6 cells, an effect that was blocked by the inhibitors of PKCalpha (Gö6976) and PKCe (eV1-2). In addition, the pretreatment with the inhibitor of ERK1/2 (PD98059) prevented the mitogenic activity induced by treatment with PMA for 15 min.
  
  
  CONCLUSIONS
  We demonstrated that the activation of PKCalpha and PKCe by phorbol ester in tumor pituitary GH3B6 cells led to cell proliferation and cell cycle progression, effects that involved ERK1/2 activation.
authors.affiliation: Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina. jpetiti@cmefcm.uncor.edu
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Petiti
authors.forename: Silvina
authors.initials: S
authors.lastname: Gutiérrez
authors.forename: Ana Lucía
authors.initials: AL
authors.lastname: De Paul
authors.forename: Verónica
authors.initials: V
authors.lastname: Andreoli
authors.forename: Claudia Mariela
authors.initials: CM
authors.lastname: Palmeri
authors.forename: Liliana Del Valle
authors.initials: Ldel V
authors.lastname: Sosa
authors.forename: José Luis
authors.initials: JL
authors.lastname: Bocco
authors.forename: Alicia Inés
authors.initials: AI
authors.lastname: Torres
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D010911:Pituitary Neoplasms / Q000201:enzymology*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D005419:Flavonoids; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D001973:Bromodeoxyuridine; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one