Cyclin D1 expression is induced by viral BARF1 and is overexpressed in EBV-associated gastric cancer
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Cyclin D1 expression is induced by viral BARF1 and is overexpressed in EBV-associated gastric cancer. / Wiech, Thorsten; Nikolopoulos, Elisabeth; Lassman, Silke; Heidt, Timo; Schöpflin, Anja; Sarbia, Mario; Werner, Martin; Shimizu, Yuko; Sakka, Emna; Ooka, Tadamasa; zur Hausen, Axel.
In: VIRCHOWS ARCH, Vol. 452, No. 6, 01.06.2008, p. 621-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cyclin D1 expression is induced by viral BARF1 and is overexpressed in EBV-associated gastric cancer
AU - Wiech, Thorsten
AU - Nikolopoulos, Elisabeth
AU - Lassman, Silke
AU - Heidt, Timo
AU - Schöpflin, Anja
AU - Sarbia, Mario
AU - Werner, Martin
AU - Shimizu, Yuko
AU - Sakka, Emna
AU - Ooka, Tadamasa
AU - zur Hausen, Axel
PY - 2008/6/1
Y1 - 2008/6/1
N2 - 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.
AB - 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.
KW - Cell Line
KW - Cyclin D
KW - Cyclins
KW - Epstein-Barr Virus Infections
KW - Gene Expression Profiling
KW - Humans
KW - Oligonucleotide Array Sequence Analysis
KW - Stomach Neoplasms
KW - Transfection
KW - Up-Regulation
KW - Viral Proteins
U2 - 10.1007/s00428-008-0594-9
DO - 10.1007/s00428-008-0594-9
M3 - SCORING: Journal article
C2 - 18437417
VL - 452
SP - 621
EP - 627
JO - VIRCHOWS ARCH
JF - VIRCHOWS ARCH
SN - 0945-6317
IS - 6
ER -
