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PKC-mediated survival signaling in breast carcinoma cells: a role for MEK1-AP1 signaling.
Weldon, Christopher B; McKee, Amy; Collins-Burow, Bridgette M; Melnik, Lilia I; Scandurro, Aline B; McLachlan, John A; Burow, Matthew E; Beckman, Barbara S.
Afiliação
  • Weldon CB; Department of Surgery, Tulane University School of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Int J Oncol ; 26(3): 763-8, 2005 Mar.
Article em En | MEDLINE | ID: mdl-15703835
The ability of peptide hormones, as well as the protein kinase C (PKC)-activating phorbol ester (PMA), to protect cells from apoptosis has been demonstrated to occur through activation of cellular signaling pathways such as the mitogen-activated protein kinase (MAPK) and phosphatidyl-inositol-3 kinase (PI3K) families. Here we demonstrate that tumor necrosis factor alpha (TNF)-induced apoptosis is suppressed by treatment with PMA in MCF-7 breast carcinoma cells. Reversal of the PMA survival effect with the classical isoform-specific PKC inhibitor, Go 6976, or the selective mitogen-activated protein kinase kinase (MEK) inhibitor, PD 098059, suggested a partial requirement for PKCalpha and the Erk cascade in MCF-7 cell survival. The ability of these agents to block PMA-mediated cell survival was also correlated with a suppression of PMA-induced AP-1 activity. Some naturally occurring flavonoid compounds such as apigenin can function to block cell signaling cascades such as MAPK. The ability of apigenin to block PMA-mediated cell survival was similarly correlated with suppression of PMA-stimulated AP-1 activity. Our results strongly suggest that PKC- and Erk-dependent pathways are critical components of the cell survival cascade function in suppression of TNF-induced apoptosis in MCF-7 cells. The ability of natural dietary flavonoids such as apigenin to affect cell survival pathways may represent an important aspect of the proposed anti-tumor effects of these compounds.
Assuntos
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Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Neoplasias da Mama / Sobrevivência Celular / Apoptose / MAP Quinase Quinase 1 Limite: Female / Humans Idioma: En Ano de publicação: 2005 Tipo de documento: Article
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Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Neoplasias da Mama / Sobrevivência Celular / Apoptose / MAP Quinase Quinase 1 Limite: Female / Humans Idioma: En Ano de publicação: 2005 Tipo de documento: Article