ArticleOncogene2001
Expression of herstatin, an autoinhibitor of HER-2/neu, inhibits transactivation of HER-3 by HER-2 and blocks EGF activation of the EGF receptor.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 59 citations in OpenAlex.
- Soluble isoforms of EGFR family in breast cancer: Advances and clinical relevance (Review).Oncology letters · 2026Review
- An overview of vital functions of human ecdysoneless (ECD), a highly conserved protein.Bioscience reports · 2025Review
- Intron-Encoded Domain of Herstatin, An Autoinhibitor of Human Epidermal Growth Factor Receptors, Is Intrinsically Disordered.Frontiers in molecular biosciences · 2022Article
- HER2-PI9 and HER2-I12: two novel and functionally active splice variants of the oncogene HER2 in breast cancer.Journal of cancer research and clinical oncology · 2021Article
- The Mammalian Ecdysoneless Protein Interacts with RNA Helicase DDX39A To Regulate Nuclear mRNA Export.Molecular and cellular biology · 2021Article
- HER2 splice variants in breast cancer: investigating their impact on diagnosis and treatment outcomes.Oncotarget · 2020Review
- Review
- How is Herstatin, a tumor suppressor splice variant of the oncogene HER2, regulated?RNA biology · 2017Article
- Article
- Analysis of different HER-2 mutations in breast cancer progression and drug resistance.Journal of cellular and molecular medicine · 2015Review
- Suppression of heregulin β signaling by the single N-glycan deletion mutant of soluble ErbB3 protein.The Journal of biological chemistry · 2013Article
- Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance.International journal of cell biology · 2013Article
- Expression and roles of Wilms' tumor 1-associating protein in glioblastoma.Cancer science · 2012Article
- The peptide derived from erbB2 auto-inhibitor herstatin shared in the same epitope and function with functional antibody 2C4.Molecular biotechnology · 2012Article
- Mechanisms of ErbB receptor negative regulation and relevance in cancer.Experimental cell research · 2009Review
- The ERBB3 receptor in cancer and cancer gene therapy.Cancer gene therapy · 2008Review
- A splice variant of HER2 corresponding to Herstatin is expressed in the noncancerous breast and in breast carcinomas.Neoplasia (New York, N.Y.) · 2008Article
- ErbB receptor negative regulatory mechanisms: implications in cancer.Journal of mammary gland biology and neoplasia · 2006Review
- Negative regulation of ErbB family receptor tyrosine kinases.British journal of cancer · 2004Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The four members of the EGF receptor family are capable of homomeric as well as heteromeric interactions. HER-2/neu (erbB-2) dominates as the preferred coreceptor that amplifies mitogenic signaling. An alternative HER-2/neu product, herstatin, consists of a segment of the ectodomain of p185HER-2 and an intron-encoded C-terminus. Recombinant herstatin was found to bind with nM affinity and inhibit p185HER-2. To further examine the impact on receptor activity, herstatin was expressed with various receptor tyrosine kinases. In CHO cells that overexpressed HER-2, herstatin caused a sevenfold inhibition of colony formation that corresponded to a reduction in the tyrosine phosphorylation of p185HER-2. Herstatin also prevented HER-2 mediated transactivation of the kinase impaired HER-3 as reflected in transphosphorylation of HER-3 and heteromers between HER-2 and HER-3. In EGF receptor-overexpressing cells, EGF induction of receptor dimerization and tyrosine phosphorylation were reduced more than 90%, and receptor down-regulation as well as colony formation were also suppressed by coexpression with herstatin. Inhibition was selective for the EGF receptor family since herstatin expression did not reduce tyrosine phosphorylation mediated by the FGF receptor-2 or by insulin-like growth factor -1. Herstatin bound to the EGF receptor as well as to p185HER-2 in pull-down assays suggesting that complex formation may be involved in receptor inhibition. Our findings indicate that herstatin has the capability to negatively regulate combinations of interactions between group I receptor tyrosine kinases that confer synergistic growth signals.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.