Protein kinase C-α downregulates estrogen receptor-α by suppressing c-Jun phosphorylation in estrogen receptor-positive breast cancer cells

  • Authors:
    • Sangmin Kim
    • Jeongmin Lee
    • Se Kyung Lee
    • Soo Youn Bae
    • Jiyoung Kim
    • Minkuk Kim
    • Won Ho Kil
    • Seok Won Kim
    • Jeong Eon Lee
    • Seok Jin Nam
  • View Affiliations

  • Published online on: December 19, 2013     https://doi.org/10.3892/or.2013.2936
  • Pages: 1423-1428
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Abstract

Protein kinase C (PKC) activity is elevated in malignant compared with that in normal human breast tissue. In the present study, we investigated the regulatory mechanism and the co-relationship between PKC-α and estrogen receptor-α (ER-α) in ER-α-positive and tamoxifen-resistant (TAMR) breast cancer cells. Our results showed that the level of ER-α expression was significantly decreased in TAMR when compared with that in tamoxifen-sensitive (TAMS) breast cancer cells. However, PKC-α phosphorylation was increased in TAMR breast cancer cells when compared to that in TAMS breast cancer cells. Additionally, ER-α expression was significantly decreased due to the overexpression of constitutively active PKC-α (CA-PKC-α). Next, we investigated the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), a reversible activator of PKC, on ER-α expression in ER-α-positive breast cancer cells. TPA decreased the levels of ER-α expression in a time- and dose-dependent manner. In contrast, the TPA-induced downregulation of ER-α was prevented by Go6983, a specific PKC inhibitor. Notably, we found that CA-PKC-α suppressed c-JUN phosphorylation, which is a major activating protein-1 factor, and TPA-induced downregulation of ER-α was prevented by SR11302, a specific activator protein-1 inhibitor. Taken together, we demonstrated that PKC-α activity suppressed the level of ER-α expression by inhibiting c-JUN phosphorylation in ER-α-positive breast cancer cells. Therefore, we suggest that PKC-α may be a potential therapeutic target for treating ER-positive and TAMR breast cancer.
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2014-March
Volume 31 Issue 3

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

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Spandidos Publications style
Kim S, Lee J, Lee SK, Bae SY, Kim J, Kim M, Kil WH, Kim SW, Lee JE, Nam SJ, Nam SJ, et al: Protein kinase C-α downregulates estrogen receptor-α by suppressing c-Jun phosphorylation in estrogen receptor-positive breast cancer cells. Oncol Rep 31: 1423-1428, 2014
APA
Kim, S., Lee, J., Lee, S.K., Bae, S.Y., Kim, J., Kim, M. ... Nam, S.J. (2014). Protein kinase C-α downregulates estrogen receptor-α by suppressing c-Jun phosphorylation in estrogen receptor-positive breast cancer cells. Oncology Reports, 31, 1423-1428. https://doi.org/10.3892/or.2013.2936
MLA
Kim, S., Lee, J., Lee, S. K., Bae, S. Y., Kim, J., Kim, M., Kil, W. H., Kim, S. W., Lee, J. E., Nam, S. J."Protein kinase C-α downregulates estrogen receptor-α by suppressing c-Jun phosphorylation in estrogen receptor-positive breast cancer cells". Oncology Reports 31.3 (2014): 1423-1428.
Chicago
Kim, S., Lee, J., Lee, S. K., Bae, S. Y., Kim, J., Kim, M., Kil, W. H., Kim, S. W., Lee, J. E., Nam, S. J."Protein kinase C-α downregulates estrogen receptor-α by suppressing c-Jun phosphorylation in estrogen receptor-positive breast cancer cells". Oncology Reports 31, no. 3 (2014): 1423-1428. https://doi.org/10.3892/or.2013.2936