Hydrogen peroxide promotes transformation of rat liver non‐neoplastic epithelial cells through activation of epidermal growth factor receptor

Abstract

Previous studies demonstrated that hydrogen peroxide (H₂O₂) is a tumor promoter in the rat liver epithelial cell line T51B. We investigated the pathway linking H₂O₂ to tumor promotion. H₂O₂ can directly induce tyrosine phosphorylation of epidermal growth factor receptor (EGFR). H₂O₂ and epidermal growth factor exerted similar effects on the induction of early growth response genes, disruption of gap junction communication, triggering of calcium inflow, and promotion of transformation. Furthermore, the effect of H₂O₂ on tumor promotion was blocked by abrogation of EGFR activation. Our results suggested that tumor promotion by H₂O₂ is mediated mainly through activation of EGFR in T51B cells.