PMID- 28419472 OWN - NLM STAT- MEDLINE DCOM- 20170914 LR - 20180130 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 141 IP - 2 DP - 2017 Jul 15 TI - Hepatic expression of oncogenes Bmi1 and Dkk1 is up-regulated in hepatitis B virus surface antigen-transgenic mice and can be induced by treatment with HBV particles or lipopolysaccharides in vitro. PG - 354-363 LID - 10.1002/ijc.30742 [doi] AB - Previous studies have shown that hepatocellular carcinoma (HCC) develops more frequently in hepatitis B virus surface antigen (HBsAg)-transgenic mice (Alb/HBs) than in wild-type (WT) mice. However, the mechanism of this HCC model has not been well documented. Toll-like receptor 4 (Tlr4) signaling probably links innate immunity and HCC progression. This study was designed to investigate the role of innate immunity in hepatocarcinogenesis in Alb/HBs mice. Immunohistochemical analysis of liver specimens from Alb/HBs mice (16 per group) showed that the oncogenes Bmi1 (16/16, 100%) and Dkk1 (13/16, 81.25%) were highly expressed in Alb/HBs mice, whereas the other oncogenes evaluated were expressed in smaller percentages of mice (Afp, 9/16, 56.2%; Ctnnb1, 5/16, 31.3%; Epcam, 0/16; 0%). Comparable results were obtained by quantitative PCR analysis. Hepatic gene expression of Tlr2, Tlr4, Il6 and Tnf was additionally elevated in Alb/HBs mice. Stimulation of primary murine hepatocytes with cell culture-derived HBV particles or LPS increased the expression of oncogenes (Bmi1, Dkk1) and inflammatory factors (Tnf, Il6, Tlr4). Proliferation and colony formation of hepatoma cells were enhanced by treatment with HBV and LPS and were impaired by the suppression of Bmi1 and Dkk1 by small interfering RNAs. Substantial induction of BMI1 and DKK1 was found in liver biopsy samples from patients with HBV-related HCC but not in HCC samples without HBV infection background. These findings suggest that innate immunity may link inflammation and tumor progression during chronic HBV infection, involving the oncogenes BMI1 and DKK1. CI - (c) 2017 UICC. FAU - Zhang, Rui AU - Zhang R AD - Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Germany. AD - Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Real, Catherine I AU - Real CI AD - Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Germany. FAU - Liu, Chao AU - Liu C AD - Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Baba, Hideo A AU - Baba HA AD - Department of Pathology and Neuropathology, University Hospital Essen, University Duisburg-Essen, Germany. FAU - Gerken, Guido AU - Gerken G AD - Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Germany. FAU - Lu, Mengji AU - Lu M AD - Institute of Virology, University Hospital Essen, University Duisburg-Essen, Germany. FAU - Broering, Ruth AU - Broering R AUID- ORCID: 0000-0002-7125-3246 AD - Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170508 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (BMI1 protein, human) RN - 0 (DKK1 protein, human) RN - 0 (Hepatitis B Surface Antigens) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lipopolysaccharides) RN - EC 2.3.2.27 (Polycomb Repressive Complex 1) SB - IM MH - Animals MH - Carcinoma, Hepatocellular/genetics/immunology/metabolism/*virology MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Gene Expression Regulation, Neoplastic MH - Hep G2 Cells MH - Hepatitis B Surface Antigens/*genetics/metabolism MH - Hepatocytes/cytology/drug effects/metabolism/virology MH - Humans MH - Immunity, Innate MH - Intercellular Signaling Peptides and Proteins/genetics/*metabolism MH - Lipopolysaccharides/pharmacology MH - Liver Neoplasms/genetics/immunology/metabolism/*virology MH - Mice MH - Mice, Transgenic MH - Polycomb Repressive Complex 1/genetics/*metabolism MH - *Up-Regulation MH - Virion/pathogenicity OTO - NOTNLM OT - HBsAg OT - HCC OT - LPS OT - hepatocellular carcinoma OT - innate immunity EDAT- 2017/04/19 06:00 MHDA- 2017/09/15 06:00 CRDT- 2017/04/19 06:00 PHST- 2016/07/12 00:00 [received] PHST- 2017/04/03 00:00 [accepted] PHST- 2017/04/19 06:00 [pubmed] PHST- 2017/09/15 06:00 [medline] PHST- 2017/04/19 06:00 [entrez] AID - 10.1002/ijc.30742 [doi] PST - ppublish SO - Int J Cancer. 2017 Jul 15;141(2):354-363. doi: 10.1002/ijc.30742. Epub 2017 May 8.