Open Access

Alterations of cell cycle control proteins SHP‑1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells

  • Authors:
    • Gang Peng
    • Ru‑Bo Cao
    • Yue‑Hua Li
    • Zhen‑Wei Zou
    • Jing Huang
    • Qian Ding
  • View Affiliations

  • Published online on: August 7, 2014     https://doi.org/10.3892/mmr.2014.2463
  • Pages: 1709-1716
  • Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The primary treatment for nasopharyngeal carcinoma (NPC) is radiotherapy, with or without concurrent chemotherapy. However, resistance to radiotherapy is not uncommon. The aim of the present study was to establish a radioresistant NPC cell line to study the molecular mechanisms of radioresistance by measuring the expression of cell cycle control proteins src homology 2 domain‑containing phosphatase (SHP)‑1/2, p16, CDK4 and cyclin D1. Human nasopharyngeal carcinoma CNE‑2 cells were cultured, divided into two groups (CNE‑2S1 and CNE‑2S2) and irradiated with a dose of 6 Gy x5 or 2 Gy x15, respectively. The cells were subcultured between doses of irradiation. The surviving sublines (CNE‑2S1 and CNE‑2S2 clones) were then passaged for three months and their radiosensitivity was determined. The cell cycle distribution and protein expression of SHP‑1/2, p16, CDK4 and cyclin D1 in parental and progenitor cell lines were measured. Small interfering (si)RNA‑mediated knockdown of SHP‑1 and SHP‑2 in the NPC cells was used to further examine their roles in radiosensitivity and cell cycle distribution. CNE‑2S1, a radio‑resistant cell line, had a significantly higher percentage of cells in S phase and a lower percentage of cells in G1 phase, enhanced expression levels of SHP‑1, CDK4 and cyclin D1, and reduced expression of p16, respectively, as compared with the parent cells. Stable suppression of SHP‑1 mRNA in CNE‑2 cells resulted in increased radiosensitivity compared with the parental cells, a decrease in the number of cells in S phase and an increase in the expression of p16. The results suggested that the SHP‑1/p16/cyclin D1/CDK4 pathway may have a role in regulating radiosensitivity and cell cycle distribution in nasopharyngeal cells.
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October 2014
Volume 10 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Peng G, Cao RB, Li YH, Zou ZW, Huang J and Ding Q: Alterations of cell cycle control proteins SHP‑1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells. Mol Med Rep 10: 1709-1716, 2014
APA
Peng, G., Cao, R., Li, Y., Zou, Z., Huang, J., & Ding, Q. (2014). Alterations of cell cycle control proteins SHP‑1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells. Molecular Medicine Reports, 10, 1709-1716. https://doi.org/10.3892/mmr.2014.2463
MLA
Peng, G., Cao, R., Li, Y., Zou, Z., Huang, J., Ding, Q."Alterations of cell cycle control proteins SHP‑1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells". Molecular Medicine Reports 10.4 (2014): 1709-1716.
Chicago
Peng, G., Cao, R., Li, Y., Zou, Z., Huang, J., Ding, Q."Alterations of cell cycle control proteins SHP‑1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells". Molecular Medicine Reports 10, no. 4 (2014): 1709-1716. https://doi.org/10.3892/mmr.2014.2463