Binding, internalization, and degradation of epidermal growth factor by Balb 3T3 and BP3T3 cells: Relationship to cell density and the stimulation of cell proliferation

Abstract

Epidermal growth factor (EGF) stimulates the growth of both benzo[a]pyrene‐transformed Balb 3T3 cells (BP3T3) and untransformed Balb 3T3 cells. We describe here the binding, internalization, and degradation of [¹²⁵I]‐EGF by BP3T3 cells and 3T3 cells. Binding of [¹²⁵I]‐EGF reaches a maximum after 45 to 90 minutes incubation at 37°C. In both BP3T3 and 3T3 cells the extent of EGF binding required to stimulate DNA synthesis is density dependent; sparse cultures require a 15‐30% occupancy to elicit a maximal response whereas dense cultures require a 70‐85% occupancy. At physiological concentrations the total binding of [¹²⁵I]‐EGF to 3T3 cells is higher than to BP3T3 cells, and this difference increases at higher cell densities. The rate of degradation of [¹²⁵I]‐EGF is directly proportional to the total [¹²⁵I]‐EGF binding in each cell type. This supports the hypothesis that one cause of the diminished serum requrement of BP3T3 cells is a reduced rate of utilization of serum growth factors.