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Assignment of heregulin (HGL) to human chromosome 8p22-p11 by PCR analysis of somatic cell hybrid DNA

Journal Article · · Genomics; (United States)
;  [1]
  1. Genentech, Inc., South San Francisco, CA (United States)
Heregulin is a recently described ligand and specific activator of the receptor tyrosine kinase designated HER2 (also called erbB2 or neu). Heregulin is a secreted 45-kDa protein that contains a region with amino acid sequence similarity to epidermal growth factor (EGF). The receptors for heregulin and EGF are encoded by related protooncogenes that can produce cellular transformation and are associated with human malignancies. The overexpression of HER2 correlates with a poor prognosis in breast, ovarian, and other cancers. Heregulin was purified from the conditioned medium of a human breast cancer cell line. The isolation of cDNA clones encoding heregulin show that several alternatively spliced variants of the protein are produced. The mature protein is derived from the N-terminal half of a 640-amino-acid precursor that includes a hydrophobic domain that may anchor the precursor in the cell membrane. Recombinantly produced heregulin stimulates the tyrosine phosphorylation of HER2 in a number of cell lines and augments the proliferation of the HER2-overexpressing cell line, SK-BR-3. Heregulin mRNA is expressed in many human tissues including breast, brain, ovary, testis, small intestine, and others. The rat homologue of heregulin has also been isolated, and cDNA clones encoding this protein have been described. The rat protein has been termed Neu differentiation factor based on its ability to induce the differentiation of a mammary tumor cell line. The gene for heregulin was mapped to human chromosome 8 by PCR amplification using primers specific for human but not rodent DNA in somatic cell hybrids.
OSTI ID:
6975349
Journal Information:
Genomics; (United States), Journal Name: Genomics; (United States) Vol. 16:3; ISSN GNMCEP; ISSN 0888-7543
Country of Publication:
United States
Language:
English