Regulation of expression and transforming ability of the c-erbB-2 gene

The human c-erbB-2 gene encodes a growth factor receptor-like protein that is highly homologous to the epidermal growth factor (EGF) receptor. Previous studies have shown that the c-erbB-2 gene is preferentially expressed in fetal epithelial cells, suggesting that the ligand of the gene product controls the growth of these cells. Molecular analysis of the c-erbB-2 promoter region revealed three regulatory systems: they are a typical set of CCAAT and TATA boxes, GC boxes, and Myb binding sites. Binding of the c-myb and B-myb gene products to the promoter region seems to down-regulate the c-erbB-2 mRNA synthesis. Elevated expression of this gene is often associated with adenocarcinomas such as breast cancers and stomach cancers and is correlated with the spread of the former. Involvement of the c-erbB-2 gene in the tumor development is further demonstrated by induction of B-lymphomas in transgenic mice carrying normal or mutated forms of this c-erbB-2 gene. In addition, the transforming potential of the c-erbB-2 gene is closely correlated with elevated tyrosine kinase activity of the gene product, which is negatively regulated by its carboxy-terminal sequence of about 230 amino acid residues.