UVC modulation of epidermal growth factor receptor number in HeLa S3 cells.
Induction of transforming growth factor alpha (TGF alpha) in human cell lines by 254 nm ultraviolet radiation (UVC) suggests that TGF alpha may have an autocrine role in UV-induced tumorigenesis. Binding of TGF alpha to epidermal growth factor receptor (EGFR) is an important initial step in transducing the signal for cell division. Experiments reported herein were designed to determine whether, in addition to inducing TGF alpha, UVC might also induce changes in the levels of EGFR on HeLa S3 cells [125I]EGF binding to HeLa S3 cells was inhibited 8 h after exposure to 7 J/m2 UVC radiation followed by increased [125I]EGF binding 16-32 h after irradiation. Scatchard analysis of EGF binding at 28 h indicated that irradiated cells had 60% more receptors with no differences in apparent binding affinities (56,300 +/- 5494 receptors versus 34,900 +/- 1899 receptors in sham-irradiated cells). Cell cycle analysis at 8 h post-UVC indicated that cells had slowed traverse of S-phase, but by 24 and 48 h, times at which increases in [125I]EGF were evident, cell cycle distributions were essentially back to normal. These results indicate that UVC modulates EGFR numbers in HeLa S3 cells and suggest that solar radiation may modulate EGFR numbers in keratinocytes or other cells in the skin. The presence of UV-induced growth factors such as TGF alpha and increased levels of EGFR may result in sustained cell proliferation by autocrine or paracrine mechanisms. These populations of cycling cells would then be at risk for subsequent mutational events that result in transformation to a tumorigenic state.
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Center for Photomedicine, Lovelace Medical Foundation, Albuquerque, NM 87108.
Ellem
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D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D006367:HeLa Cells / Q000528:radiation effects*; D006801:Humans; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014466:Ultraviolet Rays
D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors