Overexpression of the human c-erbB (EGF receptor) proto-oncogene fails to alter the lifespan or promote tumourigenic growth of normal and SV40- transformed human fibroblasts

E. Kolettas, Khashayarsha Khazaie, R. F. Rosenberger

Research output: Contribution to journalArticle

4 Citations (Scopus)

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
StatePublished - 1997
Externally publishedYes

Fingerprint

Proto-Oncogenes
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Fibroblasts
Growth
Transformed Cell Line
DNA
Diploidy
Nude Mice
Messenger RNA
EGF Family of Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{1059dd11292448858c50649d4b818393,
title = "Overexpression of the human c-erbB (EGF receptor) proto-oncogene 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 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.",
keywords = "c-erbB (EGF receptor) proto-oncogene, Human fibroblasts, Transformation",
author = "E. Kolettas and Khashayarsha Khazaie and Rosenberger, {R. F.}",
year = "1997",
language = "English (US)",
volume = "11",
pages = "1071--1080",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Overexpression of the human c-erbB (EGF receptor) proto-oncogene fails to alter the lifespan or promote tumourigenic growth of normal and SV40- transformed human fibroblasts

AU - Kolettas, E.

AU - Khazaie, Khashayarsha

AU - Rosenberger, R. F.

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

KW - c-erbB (EGF receptor) proto-oncogene

KW - Human fibroblasts

KW - Transformation

UR - http://www.scopus.com/inward/record.url?scp=0030876192&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030876192&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 1071

EP - 1080

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 5

ER -