Effect of epidermal growth factor on the growth and radiation sensitivity of human breast cancer cells in vitro.
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.
Wollman
R
R
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Yahalom
J
J
Maxy
R
R
Pinto
J
J
Fuks
Z
Z
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
D000911:Antibodies, Monoclonal; D003470:Culture Media; D006728:Hormones; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D005978:Glutathione