Gene-expression profiles of a hepatitis B small surface antigen-secreting cell line reveal upregulation of lymphoid enhancer-binding factor 1

J Gen Virol. 2007 Nov;88(Pt 11):2966-2976. doi: 10.1099/vir.0.83108-0.


The genome of hepatitis B virus (HBV) consists of four open reading frames, encoding the envelope proteins (Pre-S/S), the core proteins (Pre-C/C), the polymerase (P) and the transactivating X protein (X). In the sera of HBV-infected patients, hepatitis B surface antigen (HBsAg) particles without the viral genome can outnumber virions by more than 1000-fold. To analyse the interactions between HBsAg and host cells, global gene-expression profiles of a small HBsAg (SHBs)-secreting stable cell line (HepG2-S-G2) and its counterpart control cell line (HepG2-Neo-F4) were compared. Marked upregulation of lymphoid enhancer-binding factor 1 (LEF-1), a transcription factor in the Wnt pathway, was found in SHBs-expressing cells and was confirmed by interference experiments with small interfering RNA. However, compared with the control cells, HepG2-S-G2 did not show higher proliferative competence in culture or increased tumorigenesis in nude mice. A possible mechanism to explain the discrepancy between the upregulation of LEF-1 and the lack of increased tumorigenesis is SHBs expression resulting in altered expression and distribution of LEF-1 protein in cell compartments and upregulation of LEF-1 isoforms that could suppress, rather than enhance, the Wnt pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Silencing
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis B virus / metabolism*
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / biosynthesis*
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / virology
  • Oligonucleotide Array Sequence Analysis
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism


  • Hepatitis B Surface Antigens
  • Lymphoid Enhancer-Binding Factor 1
  • RNA, Small Interfering

Associated data

  • GEO/GSE4549