Modulation of hepatitis B surface antigen secretion by annexin II expressed in hepatitis B virus‑producing hepatoma cells

Liu,Yaming; Gao,Pujun

doi:10.3892/mmr.2014.2602

December-2014 Volume 10 Issue 6

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

December-2014 Volume 10 Issue 6

Full Size Image

Article

Modulation of hepatitis B surface antigen secretion by annexin II expressed in hepatitis B virus‑producing hepatoma cells

Authors:
- Yaming Liu
- Pujun Gao
View Affiliations / Copyright

Affiliations: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Pages: 3113-3117
|
Published online on: September 30, 2014

https://doi.org/10.3892/mmr.2014.2602
Expand metrics +

Abstract

The role of annexin II in hepatitis B virus (HBV)‑associated hepatocellular carcinoma (HCC) remains to be elucidated. Intracellular hepatitis B surface antigen (HBsAg)‑retention contributes to the induction of hepatocarcinogenesis. The present study aimed to investigate the regulation of HBsAg secretion by annexin II expressed in HBV‑producing hepatoma cells. The expression of annexin II was analyzed using western blot analysis in SMMC‑7721, HepG2, HepG2.2.15, 293T and Chinese hamster ovary (CHO) cells. CHO cells transfected with an annexin II plasmid were used as a positive control. The localization of annexin II and HBsAg was observed in the HepG2 and HepG2.2.15 cells using indirect immunofluorescence. HepG2.2.15 cells were transfected with a human immunodeficiency virus‑type 1 viral infectivity factor‑hemagglutinin (Vif‑HA) plasmid or a control vector and, 24 h post‑transfection, MG132 was added to the Vif‑complemented HepG2.2.15 cells. Western blot analysis was performed to detect the expression of annexin II and Vif‑HA. HepG2 cells were cotransfected with HBV and annexin II expression vectors. Western blot analysis was performed to examine the expression of annexin II and an Abbott chemiluminescence immunoassay was used to assess the levels of HBsAg. The expression of annexin II was lower in the HepG2.2.15 cells compared with the SMMC‑7721 and HepG2 cells and the fluorescence signal of annexin II in the HepG2 cells was brighter than in the HepG2.2.15 cells. Annexin II colocalized with HBsAg in the cytosol of the HepG2.2.15 cells. MG132 was not able to increase the stability of annexin II expression in HepG2.2.15 cells. Annexin II reduced the secretion of HBsAg when compared with the control‑transfected HepG2 cells. In conclusion, HBV downregulated the expression of annexin II and annexin II decreased the secretion of HBsAg in HBV‑producing hepatoma cells in favor of intracellular HBsAg storage.

View Figures

View References

1	Kourtis AP, Bulterys M, Hu DJ and Jamieson DJ: HIV-HBV coinfection - a global challenge. N Engl J Med. 366:1749–1752. 2012. View Article : Google Scholar : PubMed/NCBI
2	Arzumanyan A, Reis HM and Feitelson MA: Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer. 13:123–135. 2013. View Article : Google Scholar : PubMed/NCBI
3	Chemin I and Zoulim F: Hepatitis B virus induced hepatocellular carcinoma. Cancer Lett. 286:52–59. 2009. View Article : Google Scholar : PubMed/NCBI
4	Wang HC, Huang W, Lai MD and Su IJ: Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer Sci. 97:683–688. 2006. View Article : Google Scholar : PubMed/NCBI
5	Hsieh YH, Su IJ, Wang HC, et al: Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis. 25:2023–2032. 2004. View Article : Google Scholar : PubMed/NCBI
6	Longerich T, Haller MT, Mogler C, et al: Annexin A2 as a differential diagnostic marker of hepatocellular tumors. Pathol Res Pract. 207:8–14. 2011. View Article : Google Scholar : PubMed/NCBI
7	Paciucci R, Torà M, Díaz VM and Real FX: The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro. Oncogene. 16:625–633. 1998. View Article : Google Scholar : PubMed/NCBI
8	Singh P: Role of Annexin-II in GI cancers: interaction with gastrins/progastrins. Cancer Lett. 252:19–35. 2007. View Article : Google Scholar : PubMed/NCBI
9	Tomonaga T, Matsushita K, Yamaguchi S, et al: Identification of altered protein expression and post-translational modifications in primary colorectal cancer by using agarose two-dimensional gel electrophoresis. Clin Cancer Res. 10:2007–2014. 2004. View Article : Google Scholar
10	Chetcuti A, Margan SH, Russell P, et al: Loss of annexin II heavy and light chains in prostate cancer and its precursors. Cancer Res. 61:6331–6334. 2001.PubMed/NCBI
11	Pena-Alonso E, Rodrigo JP, Parra IC, et al: Annexin A2 localizes to the basal epithelial layer and is down-regulated in dysplasia and head and neck squamous cell carcinoma. Cancer Lett. 263:89–98. 2008. View Article : Google Scholar : PubMed/NCBI
12	Mohammad HS, Kurokohchi K, Yoneyama H, et al: Annexin A2 expression and phosphorylation are upregulated in hepatocellular carcinoma. Int J Oncol. 33:1157–1163. 2008.PubMed/NCBI
13	Yoon SY, Kim JM, Oh JH, et al: Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags. Int J Oncol. 29:315–327. 2006.PubMed/NCBI
14	Niu D, Sui J, Zhang J, et al: iTRAQ-coupled 2-D LC-MS/MS analysis of protein profile associated with HBV-modulated DNA methylation. Proteomics. 9:3856–3868. 2009. View Article : Google Scholar : PubMed/NCBI
15	Ciechanover A: The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J. 17:7151–7160. 1998. View Article : Google Scholar : PubMed/NCBI
16	Glickman MH and Ciechanover A: The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 82:373–428. 2002.PubMed/NCBI
17	Eberhard DA, Karns LR, VandenBerg SR and Creutz CE: Control of the nuclear-cytoplasmic partitioning of Annexin II by a nuclear export signal and by p11 binding. J Cell Sci. 114:3155–3166. 2001.PubMed/NCBI
18	Jing X, Piao YF, Liu Y and Gao PJ: Beta2-GPI: a novel factor in the development of hepatocellular carcinoma. J Cancer Res Clin Oncol. 136:1671–1680. 2010. View Article : Google Scholar : PubMed/NCBI
19	Liu B, Sarkis PT, Luo K, et al: Regulation of Apobec3F and human immunodeficiency virus type 1 Vif by Vif-Cul5-ElonB/C E3 ubiquitin ligase. J Virol. 79:9579–9587. 2005. View Article : Google Scholar : PubMed/NCBI
20	Niu D, Feng H and Chen WN: Proteomic analysis of HBV-associated HCC: insights on mechanisms of disease onset and biomarker discovery. J Proteomics. 73:1283–1290. 2010. View Article : Google Scholar : PubMed/NCBI
21	Laohavisit A and Davies JM: Annexins. New Phytol. 189:40–53. 2011. View Article : Google Scholar
22	Hayes MJ, Rescher U, Gerke V and Moss SE: Annexin-actin interactions. Traffic. 5:571–576. 2004. View Article : Google Scholar
23	Rescher U and Gerke V: S100A10/p11: family, friends and functions. Pflugers Arch. 455:575–582. 2008. View Article : Google Scholar : PubMed/NCBI
24	Yeung P, Wong DK, Lai CL, et al: Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B. J Infect Dis. 203:646–654. 2011. View Article : Google Scholar : PubMed/NCBI