ArticleOncogene2010
Reactivation of epigenetically silenced HER4/ERBB4 results in apoptosis of breast tumor cells.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 51 citations in OpenAlex.
- Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer.Oncotarget · 2016Trial
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- Overexpressed nicotinamide N‑methyltransferase in endometrial stromal cells induced by macrophages and estradiol contributes to cell proliferation in endometriosis.Cell death discovery · 2024Article
- CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.BMC bioinformatics · 2023Article
- The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein.Pharmacological reviews · 2022Review
- Increased VEGF-A in solid type of lung adenocarcinoma reduces the patients' survival.Scientific reports · 2021Article
- Biasing human epidermal growth factor receptor 4 (HER4) tyrosine kinase signaling with antibodies: Induction of cell death by antibody-dependent HER4 intracellular domain trafficking.Cancer science · 2020Article
- The role of ErbB4 in cancer.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- ErbB4 3'-UTR Variant (c.*3622A>G) is Associated with ER/PR Negativity and Advanced Breast Cancer.Indian journal of clinical biochemistry : IJCB · 2020Article
- VCF2CNA: A tool for efficiently detecting copy-number alterations in VCF genotype data and tumor purity.Scientific reports · 2019Article
- Application of Multiplex Ligation-Dependent Probe Amplification in Determining the Copy Number Alterations ofReports of biochemistry & molecular biology · 2019Article
- Advanced development of ErbB family-targeted therapies in osteosarcoma treatment.Investigational new drugs · 2019Review
- Frequency, impact and a preclinical study of novelTherapeutic advances in medical oncology · 2018Article
- Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression.Current genomics · 2017Review
- Overcoming resistance to HER2 inhibitors through state-specific kinase binding.Nature chemical biology · 2016Article
- Article
- Aberrant methylation of ERBB pathway genes in sporadic colorectal cancer.Journal of applied genetics · 2015Article
- Hypoxia-inducible factor-1α induces ErbB4 signaling in the differentiating mammary gland.The Journal of biological chemistry · 2014Article
- Epigenetic deregulation in pediatric acute lymphoblastic leukemia.Epigenetics · 2014Article
- LHX6 acts as a novel potential tumour suppressor with epigenetic inactivation in lung cancer.Cell death & disease · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Experimental and clinical data support a growth inhibitory role for HER4 in breast cancer. Clinically HER4 expression is extinguished during breast tumorigenesis supporting a tumor suppressor function for HER4, however, a molecular mechanism to explain the selective loss of HER4 expression has remained elusive. Epigenetic mechanisms, for example, aberrant gene promoter hypermethylation, have been shown to ablate tumor suppressor gene expression in breast carcinomas. We identified a CpG island within the HER4 promoter and show by pyrosequencing of bisulfite-treated DNA an inverse correlation between HER4 expression and the extent of promoter methylation. Treatment of the HER4-negative BT20 cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC)-enhanced HER4 expression, confirming a role for DNA methylation in suppressed HER4 expression. DAC treatment to reactive HER4 expression in combination with the HER4 ligand heregulin-β1 (HRG) resulted in apoptosis of BT20 cells providing a novel therapeutic strategy for triple-negative tumors. The BT20 cells were rescued from apoptosis when preincubated with HER4 small interfering RNA, thereby confirming a role for HER4 in DAC/HRG-induced apoptosis. We verified HER4 promoter methylation in primary breast carcinomas and detected a significant increase in HER4 promoter methylation in HER4-negative breast tumors (P<0.001). Furthermore, increased levels of HER4 promoter methylation were significantly associated with worse patient prognosis (P=0.0234). Taken together, our data support a tumor suppressor function for HER4, which is epigenetically suppressed in breast tumors through promoter hypermethylation.
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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.