Involvement of PI3K in HCV-related lymphoproliferative disorders

Anna Alisi, Carlo Giannini, Alessandra Spaziani, Patrizio Caini, Anna L. Zignego, Clara Balsano

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)396-404
Number of pages9
JournalJournal of Cellular Physiology
Volume214
Issue number2
DOIs
Publication statusPublished - Feb 2008

    Fingerprint

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Alisi, A., Giannini, C., Spaziani, A., Caini, P., Zignego, A. L., & Balsano, C. (2008). Involvement of PI3K in HCV-related lymphoproliferative disorders. Journal of Cellular Physiology, 214(2), 396-404. https://doi.org/10.1002/jcp.21211