title: Effect of epidermal growth factor on the growth and radiation sensitivity of human breast cancer cells in vitro.
abstract: OBJECTIVE
  To study the effect of epidermal growth factor (EGF) on the radiation sensitivity of MCF-7 breast cancer cells.
  
  
  METHODS
  Radiation dose survival curves were generated for MCF-7 cells under conditions of hormonal deprivation. Epidermal growth factor and/or a monoclonal antibody to its receptor (mAb-225) were added prior to irradiation. Cell cycle distribution was determined by flow cytometry and cellular glutathione (GSH) levels were measured by a glutathione reductase assay.
  
  
  RESULTS
  Under hormonal deprivation (control), more than 90% of the MCF-7 cells were arrested in G0/G1 phase and the D(o) of their survival curve was 0.66 +/- .01 Gy. The addition of EGF resulted in (a) growth stimulation; (b) increased percentage of cells in the S-phase of the cell cycle; (c) increased radioresistance (D(o) = 0.81 +/- .04 Gy; p < .05, compared with controls); (d) increased cellular GSH level. The EGF effect on radiation response was observed in a time- and dose-dependent manner. The addition of mAb-225 blocked the ability of EGF to enhance growth and radioresistance (D(o) = 0.68 +/- .03 Gy).
  
  
  CONCLUSIONS
  Epidermal growth factor stimulates the growth and when administered prior to irradiation increases the radioresistance of hormone-deprived MCF-7 cells. These effects are inhibited by a specific antibody to the EGF receptor. Epidermal growth factor concomitantly increased the fraction of S-phase cells and intracellular GSH levels. This system of growth factor-altered radiosensitivity in human breast cancer cells provides a useful model for the study of the radiation response mechanisms in human malignancy.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: R
authors.initials: R
authors.lastname: Wollman
authors.forename: J
authors.initials: J
authors.lastname: Yahalom
authors.forename: R
authors.initials: R
authors.lastname: Maxy
authors.forename: J
authors.initials: J
authors.lastname: Pinto
authors.forename: Z
authors.initials: Z
authors.lastname: Fuks
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000528:radiation effects; D003470:Culture Media; D004307:Dose-Response Relationship, Radiation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000276:immunology; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media; D006728:Hormones; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D005978:Glutathione