title: Alterations of cell cycle control proteins SHP‑1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells.
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.
authors.affiliation: Department of Head and Neck Cancer, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Head and Neck Cancer, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ru-Bo
authors.initials: RB
authors.lastname: Cao
authors.affiliation: Department of Head and Neck Cancer, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Head and Neck Cancer, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Zou
authors.affiliation: Department of Head and Neck Cancer, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Head and Neck Cancer, Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011836:Radiation Tolerance; D015854:Up-Regulation
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D034741:RNA, Small Interfering; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
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