γ-Heregulin: a fusion gene of DOC-4 and neuregulin-1 derived from a chromosome translocation

Abstract

γ-Heregulin was identified as an isoform resulting from alternate splicing of the neuregulin-1 gene, after cloning of its cDNA from the MDA-MB-175 breast cancer cell line. γ-Heregulin was shown to promote growth of cultured MDA-MB-175 cells resulting from activation of its cognate ErbB tyrosine kinase reporters. We show here that γ-heregulin is transcribed from a fusion gene resulting from a chromosome translocation in MDA-MB-175 cells. The fusion chromosome is described as dic(8:11)(8qter→8p12::11q13→11pter). As a result, the 5′ end of the γ-heregulin gene is derived from the stress-induced gene, DOC-4 (11q13), while the 3′ end is from the neuregulin-1 gene (8p12). Thus, expression of γ-heregulin is under the control of the DOC-4 promoter. By contrast with MDA-MB-175 cells, RT – PCR failed to detect a γ-heregulin transcript in either E9.5 to E13.5 embryonic mouse tissues, adult mouse tissues or other human tumour cell lines. We conclude, therefore, that γ-heregulin is not a native isoform of the neuregulin-1 gene, but a novel growth factor that may contribute to tumour cell proliferation.