Article

Hepatitis B virus protein preS2 potentially promotes HCC development via its transcriptional activation of hTERT.

Institute of Immunology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, Shandong University School of Medicine, Shandong, 250012 PR China.
Gut (impact factor: 10.11). 09/2009; 58(11):1528-37. DOI:10.1136/gut.2008.174029 pp.1528-37
Source: PubMed

ABSTRACT Telomerase is significantly reactivated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Our previous studies showed that the transactivation unit of HBV surface (S) gene, preS2, could upregulate human telomerase reverse transcriptase (hTERT) expression and telomerase activity of HepG2 cells. Here, we aim to explore the functions, and the underlying mechanisms, of this preS2-mediated hTERT upregulation during HCC development.
An antisense blocking assay was performed on HBV-integrated HepG2.2.15 cells. The expression of hTERT was examined in clinical samples to test the role of the preS2-mediated hTERT upregulation in HCC development in vivo. In order to explore the mechanisms of preS2-mediated hTERT upregulation, co-transfection, reporter assays and electrophoretic mobility shift assays (EMSA) were performed.
Blocking preS2 expression reduced hTERT expression, telomerase activity, cell proliferation and tumorigenicity of HepG2.2.15. A region located between -349 and -329 bp upstream of the transcription initiation site of hTERT was identified as responsible for the preS2-mediated effect. preS2 interacted with the preS2-responsible region (PRR) and activated the hTERT promoter. Importantly, hTERT was also highly expressed in preS2-positive human HCC samples. All these findings strongly suggest that preS2 may promote HCC development via hTERT activation.
HBV protein preS2 upregulates hTERT via the PRR element in promoting HCC development.

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    Tianzhen Wang, Ran Zhao, Yiqi Wu, Dan Kong, Lei Zhang, Di Wu, Chao Li, Chong Zhang, Zuxi Yu, Xiaoming Jin
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    Virology Journal 01/2011; 8:231. · 2.34 Impact Factor
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Keywords

-329 bp upstream
 
Blocking preS2 expression
 
clinical samples
 
electrophoretic mobility shift assays
 
HBV protein preS2 upregulates hTERT
 
HBV surface
 
HBV)-associated hepatocellular carcinoma
 
HBV-integrated HepG2.2.15 cells
 
HCC development
 
hepatitis B virus
 
HepG2 cells
 
preS2-mediated hTERT upregulation
 
preS2-positive human HCC samples
 
preS2-responsible region
 
previous studies
 
PRR element
 
reporter assays
 
telomerase activity
 
transcription initiation site
 
underlying mechanisms