Nuclear accumulation of epidermal growth factor in cultured rat pituitary cells

Abstract

Epidermal growth factor (EGF) is a mitogen for epidermal cells in vivo and for a wide variety of cells in culture. EGF can also regulate the cellular levels of various hormones and fibronectin at concentrations which only minimally influence cell division. EGF treatment of rat pituitary GH3 cells affects chromatin structure such that isolated nuclei from treated cells have an increased capacity to bind bacterial RNA polymerase in initiation site complexes. Various nuclear functions are modulated by EGF in GH3 cells despite its failure to affect DNA synthesis or cell proliferation. The nuclear accumulation of nerve growth factor (NGF) in rat pheochromocytoma PC12 cells in which NGF does not promote cell division but does influence RNA and protein synthesis while inducing overt differentiation (neurite outgrowth) was reported. The similarities between the 2 systems and the various theories regarding the mechanism by which mitogens exert their growth-promoting and other effects led to an investigation of whether an interaction between EGF and the cell nucleus can be demonstrated after surface binding and internalization of EGF in GH3 cells. When its lysosomal degradation is inhibited by chloroquine, EGF accumulates in the nucleus.