title: Overexpression of the human c-erbB (EGF receptor) protooncogene fails to alter the lifespan or promote tumourigenic growth of normal and SV40-transformed human fibroblasts.
abstract: c-erbB was introduced into normal human fibroblasts, MRC-5, which expressed normal levels of EGF receptor and in a SV40-transformed cell line, MRC-5V1, derived from them, which expressed markedly reduced levels of EGF receptor mRNA. MRC-5 overexpressing c-erbB, responded mitogenically to EGF. However, addition of high EGF concentrations markedly reduced DNA synthesis and resulted in the inhibition of cellular growth. In contrast, MRC-5V1 exhibited an increase in DNA synthesis in an EGF-dependent manner which was enhanced by overexpression of c-erbB. These cells, unlike MRC-5, also produced TGF alpha, an EGF receptor ligand which is often associated with cellular transformation. Ligand-activation of EGF receptor did not alter the lifespan, induce focus formation or anchorage-independence of MRC-5 and all the cell types remained non-tumourigenic in nude mice. However, c-erbB induced the expression of tPA, c-jun and junB in both MRC-5 and MRC-5V1. The data suggest that overexpression and activation of c-erbB is unlikely to play a role in immortalisation of human diploid fibroblasts but it may contribute to cellular transformation.
authors.affiliation: GERMAN CANC RES CTR,DIV CELLULAR IMMUNOL,D-69120 HEIDELBERG,GERMANY. NATL INST BIOL STAND & CONTROLS,MOL STRUCT LAB,S MIMMS ENG6 3QG,HERTS,ENGLAND.
authors.forename: E
authors.initials: E
authors.lastname: Kolettas
authors.forename: K
authors.initials: K
authors.lastname: Khazaie
authors.forename: R
authors.initials: R
authors.lastname: Rosenberger