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

Evangelos Kolettas, Khashayarsha Khazaie, Robert F. Rosenberger

Research output: Contribution to journalArticle

4 Scopus citations

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 TGFα, 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.

Original languageEnglish (US)
Pages (from-to)1071-1080
Number of pages10
JournalInternational journal of oncology
Volume11
Issue number5
DOIs
StatePublished - 1997

Keywords

  • Human fibroblasts
  • Transformation
  • c-erbB (EGF receptor) proto-oncogene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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