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- Title
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.
- Authors
Wang, Xiao-Zhong; Jolicoeur, Ethel M; Conte, Nathalie; Chaffanet, Max; Zhang, Yuhong; Mozziconacci, Marie-Joëlle; Feiner, Helen; Birnbaum, Daniel; Pébusque, Marie-Josèphe; Ron, David
- 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.
- Subjects
BREAST cancer; CANCER cells; CELL lines; PEPTIDES; CHROMOSOMES
- Publication
Oncogene, 1999, Vol 18, Issue 41, p5718
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1202950