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Nuclear ErbB2 expression in hepatocytes in liver disease
Paula Döring1, Diego F Calvisi2, Frank Dombrowski3
1Institute of Pathology, Universitätsmedizin Greifswald, Friedrich-Loeffler-Straße 23e, 17475, Greifswald, Germany. paula.doering@med.uni-greifswald.de.
Virchows Archiv : an International Journal of Pathology
|June 28, 2020
Summary
Nuclear ErbB2 expression in liver cells is linked to liver damage and disease severity, particularly in alcoholic steatohepatitis. This finding suggests a novel cellular stress response and a potential diagnostic marker for liver conditions.
Area of Science:
- Oncology
- Hepatology
- Molecular Biology
Background:
- ErbB2 (Epidermal Growth Factor Receptor 2) is known for its role in cancer signaling.
- ErbB2 can translocate to the nucleus, influencing DNA repair and cell cycle.
- Nuclear ErbB2 presence in hepatocytes during liver disease was previously uncharacterized.
Purpose of the Study:
- To investigate the characteristics of liver disease associated with nuclear ErbB2 translocation in hepatocytes.
- To explore the correlation between nuclear ErbB2 expression and histological liver damage.
- To understand the downstream signaling effects of nuclear ErbB2 in liver cells.
Main Methods:
- Immunohistochemical analysis of ErbB2 staining in 1125 human liver biopsy samples.
- Analysis of signaling and metabolic markers via immunohistochemistry.
- Correlation analysis between ErbB2 expression and histological parameters of liver damage.
Main Results:
- Nuclear ErbB2 expression was observed in hepatocytes across various liver diseases, most prominently in alcoholic steatohepatitis.
- Nuclear ErbB2 positivity correlated significantly with inflammatory activity, hepatocellular ballooning, and cholestasis.
- Hepatocytes with nuclear ErbB2 showed increased phospho-STAT3 and decreased estrogen receptor expression.
Conclusions:
- Hepatocellular nuclear ErbB2 expression is associated with cellular stress and may contribute to cell death resistance in toxic liver diseases.
- Nuclear ErbB2 signaling, indicated by pSTAT3 and estrogen receptor changes, is functional in stressed hepatocytes.
- Hepatocellular ErbB2 expression analysis may serve as a diagnostic tool for liver diseases.
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