Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors.

Abstract

A related DNA fragment distinct from the epidermal growth factor receptor and ERBB2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest identity of 64% and 67% to a contiguous region within the tyrosine kinase domains of the epidermal growth factor receptor and ERBB2 proteins, respectively. cDNA cloning revealed a predicted 148-kDa transmembrane polypeptide with structural features identifying it as a member of the ERBB gene family, prompting us to designate the gene as ERBB3. It was mapped to human chromosome 12q13 and was shown to be expressed as a 6.2-kilobase transcript in a variety of normal tissues of epithelial origin. Markedly elevated ERBB3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings suggest that increased ERBB3 expression, as in the case of epidermal growth factor receptor and ERBB2, may play a role in some human malignancies.