Journal article

Publication year: 2017

Pages: 52560-52570

Journal: Oncotarget

Volume number: 8

Issue number: 32

eISSN: 1949-2553

Open access status: Gold

DOI Link: https://doi.org/10.18632/oncotarget.15003

Publisher: Impact Journals

Abstract: 
Understanding of the pathophysiology of cholestasis associated carcinogenesis could challenge the development of new personalized therapeutic approaches and thus improve prognosis. Simultaneous damage might aggravate hepatic injury, induce chronic liver disease and even promote carcinogenesis. We aimed to study the effect of Hepatitis B virus surface protein (HBsAg) on cholestatic liver disease and associated carcinogenesis in a mouse model combining both impairments. Hybrids of Abcb4(-/-)and HBsAg transgenic mice were bred on fibrosis susceptible background BALB/c. Liver injury, serum bile acid concentration, hepatic fibrosis, and carcinogenesis were enhanced by the combination of simultaneous damage in line with activation of c-Jun N-terminal kinase (JNK), proto-oncogene c-Jun, and Signal transducer and activator of transcription 3 (STAT3). Activation of Protein Kinase RNA-like Endoplasmic Reticulum Kinase (PERK) and Eukaryotic translation initiation factor 2A (eIF2a) indicated unfolded protein response (UPR) in HBsAg-expressing mice and even in Abcb4(-/-)without HBsAg-expression. CONCLUSION: Cholestasis-induced STAT3-and JNK-pathways may predispose HBsAg-associated tumorigenesis. Since STAT3-and JNK-activation are well characterized critical regulators for tumor promotion, the potentiation of their activation in hybrids suggests an additive mechanism enhancing tumor incidence.

Harvard Citation style: Zahner, D., Glimm, H., Matono, T., Churin, Y., Herebian, D., Mayatepek, E., et al. (2017) Hepatitis B virus surface proteins accelerate cholestatic injury and tumor progression in Abcb4-knockout mice, Oncotarget, 8(32), pp. 52560-52570. https://doi.org/10.18632/oncotarget.15003

APA Citation style: Zahner, D., Glimm, H., Matono, T., Churin, Y., Herebian, D., Mayatepek, E., Koehler, K., Gattenloehner, S., Stinn, A., Tschuschner, A., Roderfeld, M., & Roeb, E. (2017). Hepatitis B virus surface proteins accelerate cholestatic injury and tumor progression in Abcb4-knockout mice. Oncotarget. 8(32), 52560-52570. https://doi.org/10.18632/oncotarget.15003