Hepatitis B virus X protein induced expression of the Nur77 gene

Hepatitis B virus (HBV) X protein (HBx) plays an essential role in developm ent of HBV-associated hepatocellular carcinoma (HCC). Recently, we reported that HBx induces Fas Ligand (FasL) expression, which may help HCC cells to evade host-immune surveillance. The aim of this study was to investigate t he role of HBx in expression of Nur77, an orphan nuclear receptor implicate d in the upregulation of FasL. When Chang X-34 expressing HBx under the con trol of a doxycycline-inducible promoter was examined, induction of Nur77 w as observed following HBx expression. Blocking of Nur77 function by introdu ction of an antisense or a dominant negative mutant Nur77 significantly inh ibited the induction of FasL, indicating that Nur77 plays critical roles in FasL expression. Further, a high-level expression of transcripts and DNA b inding of Nur77 were observed in the HBV-integrated cell lines established from HCC patients that express HBx. These results suggested that Nur77 may contribute to leading the HBx-induced Fas/FasL signaling pathway which elim inates invading Fas-expressing lymphocytes. (C) 2001 Academic Press.