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

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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.

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We like to acknowledge the excellent technical assistance of Mrs. Bokla and Deepa Pantulu, both from the Institute of Pathology, University Hospital Freiburg, Germany. We thank Axel Walch for helpful discussions with cyclin D1 FISH analyses.

Conflict of interest statement

None declared.

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Correspondence to Axel zur Hausen.

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Wiech, T., Nikolopoulos, E., Lassman, S. et al. Cyclin D1 expression is induced by viral BARF1 and is overexpressed in EBV-associated gastric cancer. Virchows Arch 452, 621 (2008). https://doi.org/10.1007/s00428-008-0594-9

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  • Epstein–Barr virus
  • Gastric carcinogenesis
  • BARF1
  • Viral oncogene
  • Cyclin D1