PKC-mediated survival signaling in breast carcinoma cells: A role for MEK1-AP1 signaling

  • Authors:
    • Christopher B. Weldon
    • Amy McKee
    • Bridgette M. Collins-Burow
    • Lilia I.. Melnik
    • Aline B. Scandurro
    • John A. McLachlan
    • Matthew E. Burow
    • Barbara S.. Beckman
  • View Affiliations

  • Published online on: March 1, 2005     https://doi.org/10.3892/ijo.26.3.763
  • Pages: 763-768
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Abstract

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 α (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, Gö 6976, or the selective mitogen-activated protein kinase kinase (MEK) inhibitor, PD 098059, suggested a partial requirement for PKCα 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.

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March 2005
Volume 26 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Weldon, C.B., McKee, A., Collins-Burow, B.M., Melnik, L.I., Scandurro, A.B., McLachlan, J.A. ... Beckman, B.S. (2005). PKC-mediated survival signaling in breast carcinoma cells: A role for MEK1-AP1 signaling. International Journal of Oncology, 26, 763-768. https://doi.org/10.3892/ijo.26.3.763
MLA
Weldon, C. B., McKee, A., Collins-Burow, B. M., Melnik, L. I., Scandurro, A. B., McLachlan, J. A., Burow, M. E., Beckman, B. S."PKC-mediated survival signaling in breast carcinoma cells: A role for MEK1-AP1 signaling". International Journal of Oncology 26.3 (2005): 763-768.
Chicago
Weldon, C. B., McKee, A., Collins-Burow, B. M., Melnik, L. I., Scandurro, A. B., McLachlan, J. A., Burow, M. E., Beckman, B. S."PKC-mediated survival signaling in breast carcinoma cells: A role for MEK1-AP1 signaling". International Journal of Oncology 26, no. 3 (2005): 763-768. https://doi.org/10.3892/ijo.26.3.763