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Article

Activation of PKC‑δ in HTLV‑1‑infected T cells

  • Authors:
    • Naoki Mori
    • Chie Ishikawa
    • Masachika Senba
  • View Affiliations / Copyright

    Affiliations: Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903‑0215, Japan, Transdisciplinary Research Organization for Subtropics and Island Studies, University of the Ryukyus, Nishihara, Okinawa 903‑0213, Japan, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852‑8523, Japan
  • Pages: 1609-1618
    |
    Published online on: January 26, 2015
       https://doi.org/10.3892/ijo.2015.2848
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Abstract

Protein kinase C (PKC)‑δ is a member of the PKC family. It has been implicated in tumor suppression as well as survival of various cancers. The aggressive malignancy of T lymphocytes known as adult T‑cell leukemia (ATL) is associated with human T‑cell leukemia virus type 1 (HTLV‑1) infection. In this study, we show that HTLV‑1‑infected T cells are characterized by phosphorylation and nuclear translocation of PKC‑δ. Expression of HTLV‑1 regulatory protein Tax increased PKC‑δ phosphorylation. Blockade of PKC‑δ by rottlerin suppressed PKC‑δ phosphorylation and inhibited cell viability in HTLV‑1‑infected T‑cell lines and primary ATL cells. Rottlerin induced cell cycle arrest at the G1 phase and caspase‑mediated apoptosis of HTLV‑1‑infected T cells. Rottlerin downregulated the expression of proteins involved in G1/S cell cycle transition, cyclin D2, CDK4 and 6, and c‑Myc, resulting in dephosphorylation of retinoblastoma protein (pRb). Furthermore, rottlerin reduced the expression of important anti‑apoptotic proteins (e.g., survivin, XIAP, Bcl‑xL and c‑FLIP) and Bcl‑2 phosphorylation, and activated the pro‑apoptotic protein Bax. Our results showed that permanent activation of nuclear factor‑κB (NF‑κB) by HTLV‑1 Tax allows infected cells to escape cell cycle arrest and apoptosis and that PKC‑δ mediates Tax‑induced activation of NF‑κB. Based on these findings, new therapies designed to target PKC‑δ could be potentially useful in the treatment of ATL.
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Copy and paste a formatted citation
Spandidos Publications style
Mori N, Ishikawa C and Senba M: Activation of PKC‑δ in HTLV‑1‑infected T cells. Int J Oncol 46: 1609-1618, 2015.
APA
Mori, N., Ishikawa, C., & Senba, M. (2015). Activation of PKC‑δ in HTLV‑1‑infected T cells. International Journal of Oncology, 46, 1609-1618. https://doi.org/10.3892/ijo.2015.2848
MLA
Mori, N., Ishikawa, C., Senba, M."Activation of PKC‑δ in HTLV‑1‑infected T cells". International Journal of Oncology 46.4 (2015): 1609-1618.
Chicago
Mori, N., Ishikawa, C., Senba, M."Activation of PKC‑δ in HTLV‑1‑infected T cells". International Journal of Oncology 46, no. 4 (2015): 1609-1618. https://doi.org/10.3892/ijo.2015.2848
Copy and paste a formatted citation
x
Spandidos Publications style
Mori N, Ishikawa C and Senba M: Activation of PKC‑δ in HTLV‑1‑infected T cells. Int J Oncol 46: 1609-1618, 2015.
APA
Mori, N., Ishikawa, C., & Senba, M. (2015). Activation of PKC‑δ in HTLV‑1‑infected T cells. International Journal of Oncology, 46, 1609-1618. https://doi.org/10.3892/ijo.2015.2848
MLA
Mori, N., Ishikawa, C., Senba, M."Activation of PKC‑δ in HTLV‑1‑infected T cells". International Journal of Oncology 46.4 (2015): 1609-1618.
Chicago
Mori, N., Ishikawa, C., Senba, M."Activation of PKC‑δ in HTLV‑1‑infected T cells". International Journal of Oncology 46, no. 4 (2015): 1609-1618. https://doi.org/10.3892/ijo.2015.2848
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