GH3B6 Pituitary Tumor Cell Proliferation is Mediated by PKCα and PKCε via ERK 1/2-dependent Pathway

被引:11
|
作者
Pablo Petiti, Juan [1 ]
Gutierrez, Silvina [1 ]
Lucia De Paul, Ana [1 ]
Andreoli, Veronica [2 ]
Mariela Palmeri, Claudia [1 ]
del Valle Sosa, Liliana [1 ]
Luis Bocco, Jose [2 ]
Ines Torres, Alicia [1 ]
机构
[1] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Microscopia Elect, RA-5000 Cordoba, Argentina
[2] Univ Nacl Cordoba, Fac Ciencias Quim, CONICET, Ctr Invest Bioquim Clin & Inmunol,CIBICI, RA-5000 Cordoba, Argentina
关键词
Pituitary; Cell proliferation; PKC alpha; PKC epsilon; ERK; 1/2; PROTEIN-KINASE-C; INDEPENDENT PATHWAYS; ACTIVATION; GROWTH; CYCLE; TRANSLOCATION; MACROPHAGES; MECHANISMS; INHIBITION; EXPRESSION;
D O I
10.1159/000320519
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: In this report, we explored the role of PKC alpha and PKC epsilon as mediators of phorbol 12-myristate 13-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 PKC alpha and PKC epsilon 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 PKC alpha and PKC epsilon 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 PKC alpha (Go6976) and PKC epsilon (epsilon V1-2). In addition, the pretreatment with the inhibitor of ERK1/2 (PD98059) prevented the mitogenic activity induced by treatment with PMA for 15 min. Conclusion: We demonstrated that the activation of PKC alpha and PKC epsilon by phorbol ester in tumor pituitary GH3B6 cells led to cell proliferation and cell cycle progression, effects that involved ERK1/2 activation. Copyright (C) 2010 S. Karger AG, Basel
引用
收藏
页码:135 / 146
页数:12
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