Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells

  • Authors:
    • Zhihua Li
    • Na Wang
    • Jieyu Fang
    • Jintao Huang
    • Fen  Tian
    • Chaohong Li
    • Fukang Xie
  • View Affiliations

  • Published online on: March 15, 2012     https://doi.org/10.3892/or.2012.1728
  • Pages: 1879-1886
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Abstract

This study was designed to investigate the role of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in tamoxifen (TAM)-induced apoptosis and drug resistance in human breast cancer cells. Drug-sensitive, or estrogen receptor (ER)-positive human breast carcinoma cells (MCF-7) and the multi-drug-resistant variant (ER-negative) MCF-7/ADR cells were treated with doses of TAM for various periods of time. Cell viability and apoptosis were assessed using cell counting, DNA fragmentation and flow cytometric analysis. We found that TAM administration caused a significant increase in apoptosis of MCF-7 cells but not MCF-7/ADR cells. Western blot analysis revealed enhanced expression of PKCδ but decreased expression of PKCα in ER-positive MCF-7 cells; while ER-negative MCF-7/ADR cells had decreased levels of PKCδ and increased levels of PKCα. Interestingly, we observed that in MCF-7 cells, TAM stimulated apoptosis by promoting rapid activation of PKCδ, antagonizing downstream signaling of ERK phosphorylation; while in MCF-7/ADR cells, TAM upregulated PKCα, which promoted ERK phosphorylation. These results suggest that PKCδ enhances apoptosis in TAM-treated MCF-7 cells by antagonizing ERK phosphorylation; while the PKCα pathway plays an important role in TAM-induced drug resistance by activating ERK signaling in MCF-7/ADR cells. The combination of TAM with PKCα and ERK inhibitors could promote TAM-induced apoptosis in breast cancer cells.

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June 2012
Volume 27 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li Z, Wang N, Fang J, Huang J, Tian F, Li C and Xie F: Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells. Oncol Rep 27: 1879-1886, 2012
APA
Li, Z., Wang, N., Fang, J., Huang, J., Tian, F., Li, C., & Xie, F. (2012). Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells. Oncology Reports, 27, 1879-1886. https://doi.org/10.3892/or.2012.1728
MLA
Li, Z., Wang, N., Fang, J., Huang, J., Tian, F., Li, C., Xie, F."Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells". Oncology Reports 27.6 (2012): 1879-1886.
Chicago
Li, Z., Wang, N., Fang, J., Huang, J., Tian, F., Li, C., Xie, F."Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells". Oncology Reports 27, no. 6 (2012): 1879-1886. https://doi.org/10.3892/or.2012.1728