Expression of the c-erbB-2 Proto-Oncogene Protein in Human Breast Cancer

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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.