title: Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation.
abstract: BACKGROUND
  Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells.
  
  
  METHODS
  The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation.
  
  
  RESULTS
  A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17beta-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation.
  
  
  CONCLUSIONS
  The observation of bystander responses in breast tumour cells may offer new potential targets for radiation-based therapies in the treatment of breast cancer.
authors.affiliation: Institute of Radiation Medicine, Fudan University, No.2094 Xie-Tu Road, Shanghai 200032, PR China. clshao@shmu.edu.cn
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
authors.forename: Melvyn
authors.initials: M
authors.lastname: Folkard
authors.forename: Kathryn D
authors.initials: KD
authors.lastname: Held
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000628:therapy*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D006371:Helium / Q000627:therapeutic use*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D013629:Tamoxifen; D006371:Helium; D004958:Estradiol