Deoxycytidine kinase participates in the regulation of radiation-induced autophagy and apoptosis in breast cancer cells

  • Authors:
    • Rui Zhong
    • Bing Liang
    • Rui Xin
    • Xuanji Zhu
    • Zhuo Liu
    • Qiao Chen
    • Yufei Hou
    • Zhao Jin
    • Mu Qi
    • Shumei Ma
    • Xiaodong Liu
  • View Affiliations

  • Published online on: January 22, 2018     https://doi.org/10.3892/ijo.2018.4250
  • Pages: 1000-1010
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Abstract

Deoxycytidine kinase (dCK) is a rate limiting enzyme critical for the phosphorylation of endogenous deoxynucleosides and for the anti‑tumor activity of many nucleoside analogs. dCK is activated in response to ionizing radiation (IR) and it is required for the G2/M checkpoint induced by IR. However, whether dCK plays a role in radiation-induced autophagy and apoptosis is less clear. In this study, we reported that dCK decreased IR-induced total cell death and apoptosis, and increased IR-induced autophagy in SKBR3 and MDA‑MB‑231 breast cancer cell lines. A molecular switch exists between apoptosis and autophagy. We further demonstrated that serine 74 phosphorylation was required for the regulation of autophagy. In dCK wild‑type (WT) or dCK S74E (mutant) MDA‑MB‑231 cell models, the expression levels of phospho-Akt, phospho-mammalian target of rapamycin (mTOR) and phospho-P70S6K significantly decreased following exposure to IR. Moreover, the ratio of Bcl‑2/Beclin1 (BECN1) significantly decreased in the S74E mutant cells; however, no change was observed in the ratio of Bcl‑2/BAX. Taken together, our findings indicate that phosphorylated and activated dCK inhibits IR-induced total cell death and apoptosis, and promotes IR-induced autophagy through the mTOR pathway and by inhibiting the binding of Bcl‑2 protein to BECN1.
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March-2018
Volume 52 Issue 3

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

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Spandidos Publications style
Zhong R, Liang B, Xin R, Zhu X, Liu Z, Chen Q, Hou Y, Jin Z, Qi M, Ma S, Ma S, et al: Deoxycytidine kinase participates in the regulation of radiation-induced autophagy and apoptosis in breast cancer cells. Int J Oncol 52: 1000-1010, 2018
APA
Zhong, R., Liang, B., Xin, R., Zhu, X., Liu, Z., Chen, Q. ... Liu, X. (2018). Deoxycytidine kinase participates in the regulation of radiation-induced autophagy and apoptosis in breast cancer cells. International Journal of Oncology, 52, 1000-1010. https://doi.org/10.3892/ijo.2018.4250
MLA
Zhong, R., Liang, B., Xin, R., Zhu, X., Liu, Z., Chen, Q., Hou, Y., Jin, Z., Qi, M., Ma, S., Liu, X."Deoxycytidine kinase participates in the regulation of radiation-induced autophagy and apoptosis in breast cancer cells". International Journal of Oncology 52.3 (2018): 1000-1010.
Chicago
Zhong, R., Liang, B., Xin, R., Zhu, X., Liu, Z., Chen, Q., Hou, Y., Jin, Z., Qi, M., Ma, S., Liu, X."Deoxycytidine kinase participates in the regulation of radiation-induced autophagy and apoptosis in breast cancer cells". International Journal of Oncology 52, no. 3 (2018): 1000-1010. https://doi.org/10.3892/ijo.2018.4250