Oncogenic circuit constituted by Ser31-HBx and Akt increases risks of chronic hepatitis and hepatocellular carcinoma

Biochimica Et Biophysica Acta
Wei-Ping LeeShou-Dong Lee

Abstract

The X protein of hepatitis B virus (HBx) has been specifically implicated in the development of hepatocellular carcinoma (HCC). Clinical associations of HBx isoforms with chronic hepatitis and HCC have not been well studied. HBx has two roles in liver cells, namely pro-apoptotic and anti-apoptotic. In this report, we examined the role of Ser31-HBx in HCC and chronic hepatitis. Using the case-control study, we determined risks of chronic hepatitis and HCC conferred by hepatitis B virus (HBV) containing Ser31-HBx that was phosphorylated by Akt. Ser31-HBx isoforms conferred 3.23-fold risk of HCC in male and 3.36-fold risk in female. Ser31 isoforms were associated with 3.12-fold risk of chronic hepatitis and 3.43-fold risk of cirrhosis and also associated with higher HBV viral load and replication efficiency and lower rate of HBe loss. To determine the mechanism, we found that Ser31-HBx constituted an oncogenic circuit with Akt and cooperated with ras to transform NIH3T3 cells in contrast to non-Ser31-HBxs that did not transduce oncogenic signals. Our results give a clue to account for an underlying cause of HBx-mediated hepatocarcinogenesis. It appears that Ser31 phosphorylation of HBx by Akt plays an important role. The current s...Continue Reading

References

Jan 1, 1989·Cancer Chemotherapy and Pharmacology·M M Tomayko, C P Reynolds
Feb 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P PaterliniC Brechot
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·X W WangC C Harris
Feb 7, 1998·The Journal of Biological Chemistry·H KimY Yun
Mar 6, 1998·Molecular and Cellular Biology·I HavivY Shaul
Nov 13, 1998·Science·M H CardoneJ C Reed
Nov 1, 2001·Journal of Gastroenterology·S Murakami
Apr 18, 2002·Oncogene·Margaret AshcroftKaren H Vousden
Jun 14, 2003·The Journal of Biological Chemistry·Wen-Ling ShihShin-Lian Doong
Jan 13, 2004·Reviews in Medical Virology·Angeline Bartholomeusz, Stephan Schaefer
Feb 10, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Youliang WangXiao Yang
Jun 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Man-Young ChaWang-Shick Ryu
Aug 2, 2005·The Journal of Biological Chemistry·Alvin T C LeeCaroline G L Lee
Apr 24, 2009·Journal of Clinical Microbiology·Henry Lik-Yuen ChanJoseph Jao-Yiu Sung
Jul 8, 2009·Nature Reviews. Gastroenterology & Hepatology·Watcharasak Chotiyaputta, Anna S F Lok
Jul 16, 2010·Nature Reviews. Gastroenterology & Hepatology·Ju Dong Yang, Lewis R Roberts
Sep 21, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Chao WangHong-Yang Wang
Oct 26, 2011·World Journal of Gastroenterology : WJG·Yong-Gang WeiJia-Yin Yang
May 29, 2012·Nature Genetics·Wing-Kin SungJohn M Luk
Apr 17, 2013·International Journal of Cancer. Journal International Du Cancer·Florian EwaldManfred Jücker
Aug 29, 2013·Cancer Letters·Cheng XuLiang Qiao
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Mitsugu Shimobayashi, Michael N Hall
Aug 26, 2014·Nature Reviews. Cancer·Miao Wang, Randal J Kaufman

❮ Previous
Next ❯

Citations

Sep 8, 2018·The Journal of International Medical Research·Wei SunJinglong Chen
Apr 30, 2020·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Wen-Hui XieDan Li
Nov 26, 2018·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·R SalpiniV Svicher

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Related Papers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ning-Fang MaXin-Yuan Guan
Alcoholism, Clinical and Experimental Research
Hiroshi YotsuyanagiToshiyuki Uchikoshi
Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology
G G ChenP B S Lai
© 2022 Meta ULC. All rights reserved