ArticleThe EMBO journal1993
Cell-type specific interaction of Neu differentiation factor (NDF/heregulin) with Neu/HER-2 suggests complex ligand-receptor relationships.
Article in The EMBO journal, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 236 citations in OpenAlex.
- Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance.International journal of molecular sciences · 2022Article
- Neuregulins in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2021Article
- HER3 Differentiates Basal From Claudin Type Triple Negative Breast Cancer and Contributes to Drug and Microenvironmental Induced Resistance.Frontiers in oncology · 2020Article
- Neuregulin, an Effector on Mitochondria Metabolism That Preserves Insulin Sensitivity.Frontiers in physiology · 2020Review
- Regulation of the prometastatic neuregulin-MMP13 axis by SRC family kinases: therapeutic implications.Molecular oncology · 2017Article
- A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic targets in cancer.Oncotarget · 2017Review
- Identification of novel biomarkers for prediction of neurological prognosis following cardiac arrest.Oncotarget · 2017Article
- Differential changes in Neuregulin-1 signaling in major brain regions in a lipopolysaccharide-induced neuroinflammation mouse model.Molecular medicine reports · 2016Article
- Evaluation of the antitumor activity of dacomitinib in models of human bladder cancer.Molecular medicine (Cambridge, Mass.) · 2013Article
- ErbB2 dephosphorylation and anti-proliferative effects of neuregulin-1 in ErbB2-overexpressing cells; re-evaluation of their low-affinity interaction.Scientific reports · 2013Article
- The ERBB network: at last, cancer therapy meets systems biology.Nature reviews. Cancer · 2012Review
- EGFR/HER-targeted therapeutics in ovarian cancer.Future medicinal chemistry · 2012Review
- Cross-talk and modulation of signaling between somatostatin and growth factor receptors.Endocrine · 2011Review
- Article
- A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins.British journal of cancer · 2004Article
- Neuregulin signaling via erbB receptor assemblies in the nervous system.Molecular neurobiology · 2002Review
- Regulation of neuregulin expression in the injured rat brain and cultured astrocytes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2001Article
- Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is independent of p53.Oncogene · 2001Article
- Expression of erbB/HER receptors, heregulin and P38 in primary breast cancer using quantitative immunohistochemistry.Pathology oncology research : POR · 2001Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Neu/HER-2 receptor tyrosine kinase is overexpressed in some types of human adenocarcinomas, including tumors of the breast and the ovary. A 44 kDa glycoprotein that elevates tyrosine phosphorylation of Neu has been isolated and named Neu differentiation factor (NDF), or heregulin. Here we show that NDF affects tyrosine phosphorylation of Neu in human tumor cells of breast, colon and neuronal origin, but not in ovarian cells that overexpress the receptor. By using monoclonal antibodies (mAbs) to Neu, we found that the ovarian receptor is immunologically and biochemically similar to the mammary p185neu. Nevertheless, unlike breast-derived Neu, the ovarian protein did not display covalent cross-linking to radiolabeled NDF, and was devoid of ligand-induced association with phosphatidylinositol 3'-kinase. Direct binding analysis showed that NDF binds with high affinity (Kd approximately 10(-9) M) to mammary cells, but its weak association with ovarian cells is probably mediated by heparin-like molecules. Similar to the endogenous receptor, the ectopically overexpressed Neu of mammary cells, but not of ovarian and fibroblastic cells, exhibited elevated levels of NDF-induced phosphorylation and covalent cross-linking of the radiolabeled factor. Taken together, our results imply that NDF binding to cells requires both Neu and an additional cellular component, whose identity is still unknown, but its tissue distribution is more restricted than the expression of the neu gene.
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