title: FTS is responsible for radiation-induced nuclear phosphorylation of EGFR and repair of DNA damage in cervical cancer cells.
abstract: OBJECTIVE
  Radiation-induced nuclear stabilization and phosphorylation of epidermal growth factor receptor (EGFR) confers radioresistance. Understanding of the factor(s) regulating the nuclear stabilization and phosphorylation of EGFR is important for the modulation of radioresistance. Present study was designed to delineate the regulation of EGFR nuclear stabilization and phosphorylation by fused toes homolog (FTS), an oncoprotein, which is responsible for the radioresistance in cervical cancer cells.
  
  
  METHODS
  A cervical cancer cell line, ME180 was used. Radiation-induced change in the levels of EGFR, p-EGFR and FTS were evaluated in the cytoplasm and nucleus using Western blot analyses. FTS was silenced using siRNA-based approach. Interaction between EGFR and FTS was assessed using immunofluorescence and immunoprecipitation analyses. Double-strand breaks (DSB) of DNA were assessed using γ H2AX.
  
  
  RESULTS
  Radiation increased the levels of EGFR and FTS in the cytoplasm and nucleus. EGFR and FTS are in physical association with each other and are co-localized in the cells. FTS silencing largely reduced the nuclear stabilization and phosphorylation of EGFR and DNA-protein kinase along with increased initial and residual DSBs.
  
  
  CONCLUSIONS
  EGFR and FTS physically associate with each other and FTS silencing radiosensitizes ME180 cells through impaired nuclear EGFR signaling.
authors.affiliation: Department of Radiation Oncology, Chungbuk National University College of Medicine, 52 Naesudong-ro, Heungduk-gu, Cheongju, 361-763, Republic of Korea.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Muthusami
authors.forename: D S
authors.initials: DS
authors.lastname: Prabakaran
authors.forename: Jae-Ran
authors.initials: JR
authors.lastname: Yu
authors.forename: Woo-Yoon
authors.initials: WY
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000235:genetics* / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D006801:Humans; D047468:Immunoprecipitation; D010766:Phosphorylation / Q000528:radiation effects; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; C512478:EGFR protein, human; D066246:ErbB Receptors