The combination of epidermal growth factor and transforming growth factor-β induces novel phenotypic changes in mouse liver stem cell lines

Academic Article


  • Mouse liver stem cell (oval cell) lines were investigated in order to determine the role which two families of growth and differentiation factors (GDFs), epidermal growth factor (EGF) family and transforming growth factor beta (TGF-β) family, play in liver regeneration. EGF family members, including EGF, amphiregulin, betacellulin, heparin-binding epidermal growth factor, and TGF-alpha, were mitogenic for oval cell lines while TGF-β family members, including TGF-β1, TGF-β2 and TGF-β3, inhibited mitogenesis and induced apoptosis in oval cell lines. Surprisingly, the combination of EGF family members and TGF-β family members resulted in neither proliferation nor apoptosis but instead in a novel cellular response, cellular scattering in tissue culture and morphological differentiation in Matrigel. Analysis of the signal transduction pathways activated by exposure of oval cell lines to either EGF, EGF + TCF-β, or TGF-β indicated that novel combinations of intracellular signals result following stimulation of the cells with the combination of EGF + TGF-β. These data reveal that the dynamics of synergistic GDF action following tissue injury and regeneration results in a new level of complexity not obvious from the study of individual GDFs.
  • Published In

    Author List

  • Isfort RJ; Cody DB; Stuard SB; Randall CJ; Miller C; Ridder GM; Doersen CJ; Richards WG; Yoder BK; Erby Wilkinson J
  • Start Page

  • 3117
  • End Page

  • 3129
  • Volume

  • 110
  • Issue

  • 24