UVC modulation of epidermal growth factor receptor number in HeLa S₃ cells

Abstract

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.

Erbb2 Regulates Inflammation and Proliferation in the Skin after Ultraviolet Irradiation

“…As documented previously, 3,5,9,13,75 UV exposure resulted in the activation and up-regulation of EGFR (Figures 1B and 8B). Erbb2 receptor expression also increased after UV exposure although there is some variation in this response ( Figure 1B, Figure 8B, and data not shown).…”

“…Reactive oxygen species-mediated inactivation of receptor-associated phosphatases is believed to block receptor deactivation. 3 UV exposure also alters receptor degradation [3][4][5][6] and increases EGFR ligand expression. 7,8 Activation of EGFR by UV stimulates both MAPK and phosphatidyl inositol 3-kinase/Akt signaling.…”

RIN1 orchestrates the activation of RAB5 GTPases and ABL tyrosine kinases to determine the fate of EGFR

“…HeLa cells express physiological levels of EGFR and are a wellcharacterized model for the study of EGFR trafficking (Ley and Ellem, 1992;Rush et al, 2012). Stimulation of HeLa cells using a range of EGF concentrations caused EGFR activation, as assessed by an increase in phosphorylated ERK1 and ERK2, and high concentration EGF elicited a marked downregulation of EGFR (supplementary material Fig.…”

Chemoprevention of UV Light-Induced Skin Tumorigenesis by Inhibition of the Epidermal Growth Factor Receptor

“…EGFR activation following UV exposure is a result of both the induction of EGFR ligands and the inactivation of phosphatases that would otherwise inactivate the receptor tyrosine kinase (6)(7)(8). UV-induced activation of EGFR up-regulates several MAPK (4,9) and phosphatidylinositol 3-kinase (PI3K)/AKT (10) signaling pathways that control epidermal cell division and cell death, processes whose deregulation is critical during tumorigenesis.…”