title: Increased expression of the epidermal growth factor receptor in human epidermal keratinocytes after exposure to ionizing radiation.
abstract: The effect of exposure of human epidermal keratinocytes to ionizing radiation, both in vivo and in vitro, on the expression of the epidermal growth factor receptor (EGF-R) was studied on the protein, mRNA, and functional levels. Quantitative fluorometry of short-term organ cultures incubated with a monoclonal antibody against human EGF-R revealed a dose-dependent increase of EGF-R expression 24 h after irradiation with 4 and 6 Gy, with an additional increase after 48 h. In biopsy specimens from patients undergoing radiation therapy a markedly increased expression could be determined by quantitative fluorometry during radiation therapy which wa still considerably above the baseline level 4 weeks after termination of treatment. Radioligand binding assays demonstrated a 50% increase in 125I-EGF binding to primary keratinocytes and A431 cells, at doses of 1 Gy, with a further increase after 72 and 96 h. Northern blots were performed with total RNA from two human epidermal cell lines (SCLII and A431). In A431 cells, increased EGF-R transcript levels could be detected 48 h after irradiation. In cells of the SCLII cell line, EGF-R expression was not affected by irradiation. These results were confirmed by semiquantitative polymerase chain reaction of primary cultured keratinocytes, demonstrating an increase of transcripts of EGF-R 24 h after irradiation with single doses of 6 Gy. Thus exposure to ionizing radiation leads to an increased expression of functionally intact EGF-R in human keratinocytes, at the protein and mRNA levels, both in vitro and in vivo; we hypothesize that this effect is part of a stress program of epidermal cells in response to ionizing radiation, ensuring rapid repopulation of irradiated areas.
authors.affiliation: Institute of Radiobiology, Federal Armed Forces Medical Academy Munich, Germany.
authors.forename: R U
authors.initials: RU
authors.lastname: Peter
authors.forename: A
authors.initials: A
authors.lastname: Beetz
authors.forename: C
authors.initials: C
authors.lastname: Ried
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: D
authors.initials: D
authors.lastname: van Beuningen
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D005470:Fluorometry; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000737:chemistry / Q000528:radiation effects*; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011839:Radiation, Ionizing
chemical_list: D066246:ErbB Receptors