gamma-heregulin is the product of a chromosomal translocation fusing the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell line

gamma-heregulin is a recently described novel isoform of the heregulin/neur egulin class of EGF-like ligands that bind to and activate receptors of the ErbB family, Deregulated signaling through the heregulin-ErbB pathway is t hought to be implicated in the development of a subset of human breast canc ers. gamma-heregulin has been found to be expressed in the culture supernat ant of MDA-MB-175, a breast carcinoma cell line. gamma-heregulin is charact erized by the presence of a large N-terminal peptide extension that is not found in other heregulin isoforms, Here we report that this unique N-termin al extension of gamma-heregulin is identical to the N-terminus of DOC4, a p roduct of a recent ly identified CHOP-dependent stress-induced gene, Human DOC4 and the heregulin-encoding genes map to different chromosomes and the MDA-MB-175 cell line contains a chromosomal translocation that leads to the fusion of DOC4 and HGL, on chromosomes 11 and 8, respectively. Thus, gamma -heregulin is a product of a mutant fusion gene and not a bona fide normal isoform, We speculate that the mutation may be selected for by virtue of it s ability to activate ErbB signaling through the production of an autocrine ligand.