Involvement of PI3K in HCV-related lymphoproliferative disorders

✍ Scribed by Anna Alisi; Carlo Giannini; Alessandra Spaziani; Patrizio Caini; Anna L. Zignego; Clara Balsano

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 524 KB
• Volume: 214
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21211

✦ Synopsis

Abstract

Hepatitis C virus (HCV) core protein has been shown to deregulate cell growth and programmed cell death in hepatoma cells, but only minimal informations are available about its possible role on B‐lymphoproliferative disorders (LPDs). The aim of our work was to analyze the biological activity of HCV core protein on B‐cell proliferation. We established Wil2‐ns and Ramos B‐cell lines that stably expressed the HCV core protein. Growth curve, thymidine incorporation analysis, as well as the expression of PCNA and activated‐ERKs demonstrated that HCV core protein induced an increased growth in both cell lines. Interestingly, the HCV core protein expression determined, in our model, a downregulation of DNp73 and an upregulation of DNp63, which was essential for the maintenance of viral‐dependent effects on cell growth. Finally, we have identified phosphoinositide 3‐kinase (PI3K) as mediator of HCV core‐dependent transcriptional increase of DNp63, which in turn correlated with the increasing of lymphocyte proliferation. In primary B‐lymphocytes, derived from HCV‐related low‐grade non‐Hodgkin's lymphoma patients, consistent results were obtained. These findings provide evidence for a possible pathogenetic role played by HCV core protein in HCV‐related lymphomagenesis; it could occur through the deregulation of PI3K activity, consequent activation of Akt and overexpression of DNp63. J. Cell. Physiol. 214: 396–404, 2008. © 2007 Wiley‐Liss, Inc.