title: Knockdown of telomeric repeat binding factor 2 enhances tumor radiosensitivity regardless of telomerase status.
abstract: OBJECTIVE
  To investigate the effects of TRF2 depletion on radiosensitivity in both the telomerase-positive cell lines (A549) and alternative lengthening of telomere (ALT) cell lines (U2OS).
  
  
  METHODS
  X-ray irradiation was used to establish two radioresistant cancer models (A549R and U2OSR) from A549 and U2OS. Colony formation assay was applied to examine the radiosensitivity of radioresistant A549R and U2OSR cells and TRF2 low-expression cells. Real-time PCR and TeloTAGGG Telomerase PCR ELISA Kit were performed to examine telomere length and telomerase activity separately. γ-H2AX was detected by immunofluorescence to assess the radiation-induced DSBs.
  
  
  RESULTS
  Radioresistant cancer models were established, in which TRF2 was significantly over-expressed. Low expression of TRF2 protein could enhance the radiosensitivity and induce telomere length of A549 and U2OS cell shortening. In A549 cells with TRF2 down-regulated, the telomerase activity was inhibited, too. TRF2 deficiency increases γ-H2AX foci and fails to protect telomere from radiation.
  
  
  CONCLUSIONS
  The data suggest that TRF2 is a radioresistant protein in A549 and U2OS cells, and could potentially be a target for radiosensitization of both telomerase-positive and ALT cells in radiotherapy.
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China, yangxiaoxi827@163.com.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Yang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Han
authors.initials: H
authors.lastname: Lei
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Zhengkai
authors.initials: Z
authors.lastname: Liao
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Zhou
authors.forename: Conghua
authors.initials: C
authors.lastname: Xie
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000532:radiotherapy*; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000235:genetics; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*; D035341:Telomeric Repeat Binding Protein 2 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C468783:H2AX protein, human; D006657:Histones; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D019098:Telomerase