A FUNCTIONAL INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR IS REQUIRED FOR THE MITOGENIC AND TRANSFORMING ACTIVITIES OF THE EPIDERMAL GROWTH-FACTORRECEPTOR

When wild-type mouse embryo cells are stably transfected with a plasmi d constitutively overexpressing the epidermal growth factor (EGF) rece ptor (EGFR), the resulting cells can grow in serum-free medium supplem ented solely with EGF. Supplementation with EGF also induces in these cells the transformed phenotype (growth in soft agar). However, when t he same EGFR expression plasmid is introduced and overexpressed in cel ls derived from littermate embryos in which the insulin-like growth fa ctor I (IGF-I) receptor genes have been disrupted by homologous recomb ination, the resulting cells are unable to grow or to be transformed b y the addition of EGF. Reintroduction into these cells (null for the I GF-I receptor) of a wild-type (but not of a mutant) IGF-I receptor res tores EGF-mediated growth and transformation. Our results indicate tha t at least in mouse embryo fibroblasts, the EGFR requires the presence of a functional IGF-I receptor for its mitogenic and transforming act ivities.