Cyclin D1 expression is induced by viral BARF1 and is overexpressed in EBV-associated gastric cancer

Virchows Arch. 2008 Jun;452(6):621-7. doi: 10.1007/s00428-008-0594-9. Epub 2008 Apr 25.

Abstract

Approximately 10% of gastric carcinomas (GC) worldwide are associated with Epstein-Barr virus (EBV). GC is one of the most frequent human malignancies associated with EBV. The latent expression of the EBV-oncogene BARF1 is restricted to epithelial malignancies. To investigate the underlying BARF1-related mechanisms of oncogenic epithelial transformation, we analyzed gene expression profiles of a BARF1-transfected epithelial (HaCaT+) and the corresponding BARF1-negative (HaCaT-) cell line by cDNA microarray analysis. Real-time PCR was performed to confirm the cDNA microarray results. In addition, immunohistochemistry and fluorescence in situ hybridization were performed on a tissue microarray of 181 GC including 11 EBV-associated GC. Among other genes cyclin D1 expression was significantly upregulated in HaCaT+ on the transcriptional and protein level. Cyclin D1 protein expression in GC revealed a significant overexpression of cyclin D1 in EBV-associated GC (p<0.012) but not in EBV-negative GC. Cyclin D1 FISH showed that cyclin D1 overexpression was not due to gene amplification in EBV-associated GC. Cyclin D1 is induced in HaCaT+ by BARF1 and is overexpressed in EBV-associated GC indicating an interaction of viral BARF1 and cyclin D1.

MeSH terms

  • Cell Line
  • Cyclin D
  • Cyclins / biosynthesis*
  • Epstein-Barr Virus Infections / metabolism*
  • Gene Expression Profiling
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / virology*
  • Transfection
  • Up-Regulation
  • Viral Proteins / physiology*

Substances

  • BARF1 protein, Human herpesvirus 4
  • Cyclin D
  • Cyclins
  • Viral Proteins