國家衛生研究院 NHRI:Item 3990099045/9190

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Conference Papers/Meeting Abstract > Item 3990099045/9190

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9190

Title:	Ground glass hepatocytes coexpressing hepatitis B virus X protein and surface antigens effect on oncogenic effects and tumorigenesis
Authors:	Su, IJ;Wu, HC;Tsai, HW;Teng, CF;Hsieh, WC;Lin, YJ;Wang, LHC;Yuan, Q
Contributors:	Division of Infectious Diseases
Abstract:	Background: Hepatitis B virus (HBV) X protein (HBx) and pre-S2 deletion mutant large surface antigens have been recognized as oncoproteins that induce hepatocellular carcinoma (HCC). The interaction of these two oncoproteins in the hepatocytes and its significance in tumorigenesis remains to be elucidated. Methods: In this study, a newly developed monoclonal antibody designed specifically against HBx was used for immunohistochemical and double-labeled immunofluorescence studies and the expression of HBx and surface antigens were evaluated. In vitro studies and transgenic mice models were used to evaluate the interaction and oncogenic effects of these two viral oncoproteins. Results: We observed the co-expression of HBx with surface antigens in ground glass hepatocytes in 5 of 20 hepatitis B surface antigen positive livers. In vitro, hepatocytes co-expressing HBx and pre-S2 mutant showed an enhanced expression of vascular endothelial growth factor-A (VEGF-A), phosphorylated Akt1/2/3 (p-Akt1/2/3), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phosphorylated mammalian target of rapamycin (p-mTOR) signals. Transgenic mice harboring the double HBx and pre-S2 mutant construct plasmids developed HCCs at an average of 15.1 months, earlier than that of HBx (16.9 months) or pre-S2 mutant (24.5 months) alone. Interestingly, the oncogenic signals of VEGF-A, p-Akt1/2/3, p-ERK1/2, and p-mTOR were sequentially and differentially activated at different stages in the progression of tumorigenesis. Phosphorylated mTOR was consistently activated in transgenic and human HCCs. Conclusions: We conclude that ground glass hepatocytes co-expressing HBx and surface antigens may exhibit enhanced oncogenic effects and tumorigenesis in chronic HBV infections. The mTOR signal cascade may represent the key regulator in HBV tumorigenesis and is implicated for the design of HCC therapy.
Date:	2014-05
Relation:	Journal of Clinical Oncology. 2014 May;32(15, Suppl.):e15115.
Link to:	http://meeting.ascopubs.org/cgi/content/abstract/32/15_suppl/e15115
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0732-183X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000358613200516
Appears in Collections:	[Ih-Jen Su(2002-2015)] Conference Papers/Meeting Abstract

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