Regulation of Cell Growth by the EGF Receptor

Abstract

Epidermal growth factor (EGF) is a small protein of 53 amino acids which acts as a mitogen for various cell types in vitro and in vivo (Carpenter and Cohen 1979 and Carpenter et al., this Vol.). Several lines of evidence suggest that the receptor for this factor can also play a role in the uncontrolled proliferation characteristic of neoplastic cells. First, the v-erbB oncogene of avian erythroblastosis virus encodes a truncated EGF receptor (Downward et al. 1984) and we recently proposed that the v-erbB protein transforms by functioning as an activated growth factor receptor (see also article by Beug et al.). Second, various animal and human tumor cells produce a growth factor called transforming growth factor-α (TGF-α; Todaro et al. 1980 and article by Derynck). This growth factor is highly related to EGF; both factors bind to the EGF receptor with similar affinities and induce the proliferation of cells bearing the EGF receptor. It has been suggested that TGF-α plays a role in oncogenesis by inducing autocrine growth (Todaro et al. 1980). Finally, the EGF receptor gene is amplified and rearranged in a significant proportion of human brain tumors of glial origin (Libermann et al. 1985). The resultant overexpression of the EGF receptor may play a role in the development or progression of these tumors. Hence, it is clear that the investigation of the structure of the EGF receptor and the mechanism of its activation may provide important clues to fundamental questions underlying the mechanisms of normal growth control and neoplasia.