title: Involvement of cdc25c in cell cycle alteration of a radioresistant lung cancer cell line established with fractionated ionizing radiation.
abstract: Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R , by exposing the parental A549 cells to repeated γ-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China E-mail : conghuaxie_65@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Chun-Xu
authors.initials: CX
authors.lastname: Yang
authors.forename: Zi-Jie
authors.initials: ZJ
authors.lastname: Mei
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Zhang
authors.forename: Shao-Xing
authors.initials: SX
authors.lastname: Sun
authors.forename: Fu-Xiang
authors.initials: FX
authors.lastname: Zhou
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Zhou
authors.forename: Cong-Hua
authors.initials: CH
authors.lastname: Xie
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D020687:cdc25 Phosphatases / Q000235:genetics*
chemical_list: C517009:CDC25C protein, human; D020687:cdc25 Phosphatases