Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bargmann CI, Hung M-C, Weinberg RA (1986) Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p 185. Cell 45: 649–657
Bishop JM (1987) The molecular genetics of cancer. Science 235: 305–311
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: 1132–1139
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: 178–182
Drebin JA, Link VC, Weinberg RA, Greene MI (1986) Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. Proc Natl Acad Sci USA 83: 9129–9133
Fukushige S-I, Matsubara K-I, Yoshida M, Sasaki M, Suzuki T, Semba K, Toyoshima K, Yamamoto T (1986) Localisation of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol 6: 955–958
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 38–53
Gullick WJ, Waterfield MD (1987) Epidermal growth factor and its receptor. In: Strosberg AD (ed) The molecular biology of receptors. Ellis Horwood, Chichester, pp 15–35
Gullick WJ, Berger MS, Bennett PLP, Rothbard JB, Waterfield MD (1987) Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer 40: 246–254
Gusterson BA, Gullick WJ, Venter DJ, Powles TJ, Elliott C, Ashley S, Tidy A, Harrison S (1987) Immunohistochemical localization of c-erbB-2 in human breast carcinomas. Mol Cell Probes 1: 383–391
King CR, Kraus MH, Aaronson SA (1985) Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 229: 974–976
Lantos PL (1986) Development of nitrosourea-induced brain tumours–with a special note on changes occurring during latency. Fd Chem Toxic 24: 121–127
Meltzer SJ, Ahnen DJ, Battifora H, Yokota J, Cline MJ (1987) Proto-oncogene abnormalities in colon cancers and adenomatous polyps. Gastroenterology 92: 1174–1180
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: 976–978
Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A v-erbB related proto-oncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci USA 82: 6497–6501
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177–182
Stark GR, Wahl GM (1984) Gene amplification. Ann Rev Biochem 53: 447–491
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: 2019–2023
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: 69–72
Yamomoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K (1986) Similarity of protein encoded by the human c-erbB-2 gene to epidermal growth factor receptor. Nature 319: 230–234
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 765–766
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin · Heidelberg
About this paper
Cite this paper
Gullick, W.J. (1989). Expression of the c-erbB-2 Proto-Oncogene Protein in Human Breast Cancer. In: Eppenberger, U., Goldhirsch, A. (eds) Endocrine Therapy and Growth Regulation of Breast Cancer. Recent Results in Cancer Research, vol 113. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-83638-1_7
Download citation
DOI: https://doi.org/10.1007/978-3-642-83638-1_7
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-83640-4
Online ISBN: 978-3-642-83638-1
eBook Packages: Springer Book Archive