Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases  被引量:4

Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases

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作  者:Martina Knoess Anna Kordelia Kurz Olga Goreva Nuran Bektas Kai Breuhahn Magarethe Odenthal Peter Schirmacher Hans Peter Dienes C Thomas Bock Hanswalter Zentgraf Axel zur Hausen 

机构地区:[1]Institute of Pathology, University Hospital Cologne, Cologne, Germany [2]Department of Hematology/Oncology, Freiburg University Medical Center, Freiburg, Germany [3]Institute of Pathology, University of Heidelberg, Heidelberg, Germany [4]Department of Molecular Pathology, University Hospital Tübingen, Germany [5]German Cancer Research Center, DKFZ, Applied Tumor Virology, Heidelberg, Germany [6]Institute of Pathology, University Hospital Freiburg, Freiburg Germany

出  处:《World Journal of Gastroenterology》2006年第36期5870-5874,共5页世界胃肠病学杂志(英文版)

摘  要:AIM: To investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus (HBV) and C virus (HCV)-related liver diseases. METHODS: We generated a new monoclonal Nup88 antibody to investigate the Nup88 protein expression by immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising all stages of hepatocellular carcinogenesis. In addition, in cell culture experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma cell lines were tested for the Nup88 expression by Western-immunoblotting to test data obtained by IHC.RESULTS: Specific Nup88 expression was found in chronic HCV hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88 expression was detected in normal liver. The Nup88 expression was markedly reduced or missing in mild chronic HBV infection and inversely correlated with HBcAg expression. Irrespective of the HBV- or HCV-status, increasing Nup88 expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly expressed in hepatocellular carcinomas. The intensity of Nup88 expression significantly increased during carcinogenesis (P < 0.0001) and correlated with dedifferentiation (P < 0.0001). Interestingly, Nup88 protein expression was significantly downregulated in HBV-positive HepG2.2.15 (P < 0.002) and HB611 (P < 0.001) cell lines as compared to HBV-negative HepG2 cells. CONCLUSION: Based on our immunohistochemical data, HBV and HCV are unlikely to influence the expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an interaction of HBV with the nuclear pore in chronic hepatitis. The expression of Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non-neoplastic and neoplastic conditions of the liver.AIM: TO investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus (HBV) and C virus (HCV)- related liver diseases. METHODS: We generated a new monoclonal Nup88 antibody to investigate the Nup88 protein expression by immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising all stages of hepatocellular carcinogenesis, in addition, in cell culture experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma cell lines were tested for the Nup88 expression by Western-immunoblotting to test data obtained by IHC. RESULTS: Specific Nup88 expression was found in chronic HCV hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88 expression was detected in normal liver. The Nup88 expression was markedly reduced or missing in mild chronic HBV infection and inversely correlated with HBcAg expression, irrespective of the HBV- or HCV-status, increasing Nup88 expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly expressed in hepatocellular carcinomas. The intensity of Nup88 expression significantly increased during carcinogenesis (P 〈 0.0001) and correlated with dedifferentiation (P 〈 0.0001). interestingly, Nup88 protein expression was significantly downregulated in HBV-positive HepG2.2.15 (P 〈 0.002) and HB611 (P 〈 0.001) cell lines as compared to HBV- negative HepG2 cells. CONCLUSION: Based on our immunohistochemical data, HBV and HCV are unlikely to influence the expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an interaction of HBV with the nuclear pore in chronic hepatitis. The expression of Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non- neoplastic and neoplastic conditions of the liver.

关 键 词:Nucleoporin 88 Hepatitis B and C virus Hepatocellular carcinogenesis 

分 类 号:R512.6[医药卫生—内科学]

 

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