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Nuclear ErbB2 expression in hepatocytes in liver disease
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969555/ https://www.ncbi.nlm.nih.gov/pubmed/32591879 http://dx.doi.org/10.1007/s00428-020-02871-z |
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author | Döring, Paula Calvisi, Diego F. Dombrowski, Frank |
author_facet | Döring, Paula Calvisi, Diego F. Dombrowski, Frank |
author_sort | Döring, Paula |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00428-020-02871-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7969555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-79695552021-04-05 Nuclear ErbB2 expression in hepatocytes in liver disease Döring, Paula Calvisi, Diego F. Dombrowski, Frank Virchows Arch Original Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00428-020-02871-z) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-06-26 2021 /pmc/articles/PMC7969555/ /pubmed/32591879 http://dx.doi.org/10.1007/s00428-020-02871-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Döring, Paula Calvisi, Diego F. Dombrowski, Frank Nuclear ErbB2 expression in hepatocytes in liver disease |
title | Nuclear ErbB2 expression in hepatocytes in liver disease |
title_full | Nuclear ErbB2 expression in hepatocytes in liver disease |
title_fullStr | Nuclear ErbB2 expression in hepatocytes in liver disease |
title_full_unstemmed | Nuclear ErbB2 expression in hepatocytes in liver disease |
title_short | Nuclear ErbB2 expression in hepatocytes in liver disease |
title_sort | nuclear erbb2 expression in hepatocytes in liver disease |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969555/ https://www.ncbi.nlm.nih.gov/pubmed/32591879 http://dx.doi.org/10.1007/s00428-020-02871-z |
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