ArticleVirchows Archiv : an international journal of pathology2021
Nuclear ErbB2 expression in hepatocytes in liver disease.
Article in Virchows Archiv : an international journal of pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 14 citations in OpenAlex.
- Coronary Microvascular Dysfunction: Epidemiology, Pathophysiology, Diagnosis, and Treatment.MedComm · 2026Review
- Integrative phytochemical profiling and systems pharmacology identify ERBB2-MAPK1-AKT1 signaling as a molecular basis for the anti-vertigo effects of Ziyin Zhixuan Decoction.Biochemistry and biophysics reports · 2026Article
- Research advances in treatment strategies for breast cancer liver metastases: A comprehensive review.iLIVER · 2025Review
- MicroRNA Binding Site Polymorphisms in Hepatocellular Carcinoma: Implications for Pathogenesis, Prognosis, and Therapeutic Response.International journal of genomics · 2025Review
- p63 controls metabolic activation of hepatic stellate cells and fibrosis via an HER2-ACC1 pathway.Cell reports. Medicine · 2024Article
- New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets.Bioinformatics and biology insights · 2023Article
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3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ErbB2 is a prominent representative of the epidermal growth factor receptors that mainly attract attention as oncogenic drivers and therapeutic targets in cancer. Besides transmembrane signaling, ErbB2 may also translocate into the nucleus and mediate distinct nuclear signaling effects including DNA repair and cell cycle arrest. Unexpectedly, we found nuclear ErbB2 expression in human hepatocytes in various liver diseases so we aimed to investigate the characteristics of liver disease leading to nuclear ErbB2 translocation. The immunohistochemical pattern of ErbB2 staining was analyzed in 1125 liver biopsy samples from patients with hepatic dysfunction. Further signaling and metabolic markers were analyzed by immunohistochemistry in selected liver biopsy samples. We found a cytoplasmic and nuclear ErbB2 expression in hepatocytes from different disease conditions with the strongest expression detected in alcoholic steatohepatitis. Nuclear ErbB2 positivity significantly correlated with histologic parameters of hepatocellular damage including inflammatory activity in steatohepatitis, hepatocellular ballooning, and cholestasis. ErbB2 overexpressing hepatocytes revealed an increase of phospho-STAT3, a downstream effector of nuclear ErbB2 signaling. Notably, we observed in nuclear ErbB2-positive hepatocytes a downregulation of estrogen receptor expression. In alcoholic steatohepatitis and other toxic liver diseases, hepatocytes revealed a nuclear ErbB2 expression implying a so far unknown mechanism in hepatocytes upon cellular stress that might lead to resistance to cell death. Nuclear ErbB2-positive hepatocytes showed downregulation of estrogen receptor expression and increased levels of pSTAT3, which are signs of functionality of nuclear ErbB2 signaling. Furthermore, analysis of hepatocellular ErbB2 expression could serve as helpful tool for diagnosis of liver disease.
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