OVEREXPRESSION OF THE HUMAN C-ERBB (EGF RECEPTOR) PROTOONCOGENE FAILSTO ALTER THE LIFE-SPAN OR PROMOTE TUMORIGENIC GROWTH OF NORMAL AND SV40-TRANSFORMED HUMAN FIBROBLASTS

c-erbB was introduced into normal human fibroblasts, MRC-5, which expr essed normal levels of EGF receptor and in a SV40-transformed cell lin e, MRC-5V1, derived from them, which expressed markedly reduced levels of EGF receptor mRNA. MRC-5 overexpressing c-erbB, responded mitogeni cally to EGF. However, addition of high EGF concentrations markedly re duced 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. Thes e cells, unlike MRC-5, also produced TGF alpha, an EGF receptor ligand which is often associated with cellular transformation. Ligand-activa tion of EGF receptor did not alter the lifespan, induce focus formatio n or anchorage-independence of MRC-5 and all the cell types remained n on-tumourigenic in nude mice. However, c-erbB induced the expression o f 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.