Abstract
γ-heregulin is a recently described novel isoform of the heregulin/neuregulin class of EGF-like ligands that bind to and activate receptors of the ErbB family. Deregulated signaling through the heregulin-ErbB pathway is thought to be implicated in the development of a subset of human breast cancers. γ-heregulin has been found to be expressed in the culture supernatant of MDA-MB-175, a breast carcinoma cell line. γ-heregulin is characterized 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-terminal extension of γ-heregulin is identical to the N-terminus of DOC4, a product of a recently 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, γ-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 its ability to activate ErbB signaling through the production of an autocrine ligand.
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Acknowledgements
We thank G Schaefer and M Sliwkowski for sharing unpublished information, M Lafage-Pochitaloff for helpful discussions, J Adélaïde, A Benziane and J Simonetti for technical help. This study was supported by NCI grant CA60945 to D Ron. D Ron is a Stephen Birnbaum Scholar of the Leukemia Society of America.
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Wang, XZ., Jolicoeur, E., Conte, N. et al. γ-heregulin is the product of a chromosomal translocation fusing the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell line. Oncogene 18, 5718–5721 (1999). https://doi.org/10.1038/sj.onc.1202950
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DOI: https://doi.org/10.1038/sj.onc.1202950
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