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

Xiao Zhong Wang, Ethel M. Jolicoeur, Nathalie Conte, Max Chaffanet, Yuhong Zhang, Marie Joëlle Mozziconacci, Helen Feiner, Daniel Birnbaum, Marie Josèphe Pébusque, David Ron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5718-5721
Number of pages4
JournalOncogene
Volume18
Issue number41
DOIs
StatePublished - Oct 7 1999

Keywords

  • CHOP
  • EGF receptor
  • Signal transduction
  • Tenascin
  • Tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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