Recycling of epidermal growth factor in a human pancreatic carcinoma cell line

PANC-1 human pancreatic carcinoma cells readily bound and internalized ¹²⁵I-labeled epidermal growth factor (EGF). Bound ¹²⁵I-labeled EGF was then partially processed to a number of high molecular weight acidic species. Percoll gradient centrifugation of cell homogenates indicated that the majority of ¹²⁵I activity localized to several intracellular vesicular compartments. Both intact EGF and its processed species were subsequently released into the incubation medium. A major portion of the released radioactivity was capable of rebinding to the cell. Only a small amount of bound ¹²⁵I-labeled EGF was degraded to low molecular weight products, and this degradation was completely blocked by methylamine. This lysosomotropic compound did not arrest either the generation or the extrusion of the major high molecular weight species of processed EGF (pI 4.2). These findings suggest that in PANC-1 cells, bound EGF undergoes only limited processing. Both intact EGF and its major processed species bypass the cellular degradative pathways, are slowly released from the cell, and then rebind to the cell.