Expression of the c-erbB-2 Proto-Oncogene Protein in Human Breast Cancer
Analysis of the structure and expression of the human c-erbB-2 gene in normal and malignant cells has been stimulated by the discovery that the equivalent gene in rats, called neu,can be converted by mutation to a dominantly acting oncogene (Bargmann et al. 1986). Treatment of pregnant rats with the chemical carcinogen ethylnitrosourea (ENU) leads to the development of tumours of the central nervous system in the offspring. Despite the instability of the carcinogen, which has a half-life of about 5 min in vivo, the tumours appear with a long latency of about 200 days (Lantos 1986). In order to analyse the nature of the putative mutation caused by the alkylating agent ENU, DNA was prepared from a cell line derived from a rat brain tumour and transfected onto NIH-3T3 indicator cells. This assay revealed the presence of an activated DNA sequence that caused the recipient cells to be transformed to a malignant phenotype. Subsequent experiments showed that this was a gene related in structure to that encoding the epidermal growth factor (EGF) receptor (Coussens et al. 1985; Yamamoto 1986). Because of its derivation from a tumour classified as a neuroblastoma, the transforming oncogene was named onc-neu.
KeywordsSugar Codon Tyrosine Adenocarcinoma Catalysis
Unable to display preview. Download preview PDF.
- Coussens L, Yang-Feng TL, Liao Y-C, Chen E, Gray A, McGrath J, Seeberg PH, Liber-mann TA, Schlessinger J, Francke U, Levinson A, Ullrich A (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230: 1132–1139PubMedCrossRefGoogle Scholar
- Di Fiore PP, Pierce JH, Kraus MH, Segatto O, King CR, Aaronson SA (1987) erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science 237: 178–182Google Scholar
- Gullick WJ, Venter DJ (1988) The c-erbB-2 gene and its expression in human cancers. In: Sikora K, Waxman J (eds) The molecular biology of cancer. Blackwells, Oxford pp 38–53Google Scholar
- Gullick WJ, Waterfield MD (1987) Epidermal growth factor and its receptor. In: Strosberg AD (ed) The molecular biology of receptors. Ellis Horwood, Chichester, pp 15–35Google Scholar
- Schechter AL, Hung M-C, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, Ullrich A, Coussens L (1985) The neu gene: An erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229: 976–978Google Scholar
- Van de Vijver M, van de Bersselaar R, Devilee P, Cornelisse C, Peterse J, Nusse R (1987) Amplification of the neu (c-erbB-2) oncogene in human mammary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. Mol Cell Biol 7: 2019–2023PubMedGoogle Scholar
- Venter DJ, Tuzi NL, Kumar S, Gullick WJ (1987) Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: Immunohistological assessment correlates with gene amplification. Lancet 2: 69–72Google Scholar
- Yokota J, Yamamoto T, Toyoshima K, Terada M, Sugimura T, Battifora H, Chine MJ (1986) Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet is 765–766Google Scholar