This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kanda, T.
Right arrow Articles by Ray, R. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kanda, T.
Right arrow Articles by Ray, R. B.

 Previous Article  |  Next Article 

Journal of Virology, November 2008, p. 11066-11072, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01300-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Hepatitis C Virus Core Protein Augments Androgen Receptor-Mediated Signaling{triangledown}

Tatsuo Kanda,1 Robert Steele,1 Ranjit Ray,2,3 and Ratna B. Ray1,2,3*

Departments of Pathology,1 Internal Medicine,2 Cancer Center, Saint Louis University, St. Louis, Missouri 631043

Received 22 June 2008/ Accepted 25 August 2008

Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinoma (HCC), which is one of the male-dominant diseases. Androgen signaling in liver may be related to carcinogenesis. In this study, we investigated whether HCV proteins cross talk with the androgen receptor (AR) signaling pathway for promotion of carcinogenesis. We have demonstrated that HCV core protein alone or in context with other HCV proteins enhances AR-mediated transcriptional activity and further augments in the presence of androgen. Subsequent study suggested that HCV core protein activates STAT3, which in turn enhances AR-mediated transcription. This activity was blocked by a pharmacological inhibitor of the Jak/Stat signaling pathway, AG490. Vascular endothelial growth factor (VEGF) is a target gene of AR in liver and plays an important role in angiogenesis. Therefore, we examined whether HCV infection modulates VEGF expression in hepatocytes. Our results demonstrated that HCV enhances VEGF expression and facilitates tube formation in human coronary microvascular endothelial cells in the presence of AR. Together, our results suggest that HCV core protein acts as a positive regulator in AR signaling, providing further insight into oncogenic potential in the development of HCC in HCV-infected individuals.

* Corresponding author. Mailing address: Department of Pathology, St. Louis University, 1100 S. Grand Blvd., DRC-207, St. Louis, MO 63104. Phone: (314) 977-7822. Fax: (314) 771-3816. E-mail: rayrb{at}slu.edu

{triangledown} Published ahead of print on 3 September 2008.

Journal of Virology, November 2008, p. 11066-11072, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01300-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»