TY - JOUR
T1 - Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharynaeal carcinoma
AU - Sengupta, Srikumar
AU - Den Boon, Johan A.
AU - Chen, I. How
AU - Newton, Michael A.
AU - Dahl, David B.
AU - Chen, Meng
AU - Cheng, Yu Juen
AU - Westra, William H.
AU - Chen, Chien Jen
AU - Hildesheim, Allan
AU - Sugden, Bill
AU - Ahlquist, Paul
PY - 2006/8/15
Y1 - 2006/8/15
N2 - To identify the molecular mechanisms by which EBV-associated epithelial cancers are maintained, we measured the expression of essentially all human genes and all latent EBV genes in a collection of 31 laser-captured, microdissected nasopharyngeal carcinoma (NPC) tissue samples and 10 normal nasopharyngeal tissues. Global gene expression profiles clearly distinguished tumors from normal healthy epithelium. Expression levels of six viral genes (EBNA1, EBNA2, EBNA3A, EBNA3B, LMP1, and LMP2A) were correlated among themselves and strongly inversely correlated with the expression of a large subset of host genes. Among the human genes whose inhibition was most strongly correlated with increased EBV gene expression were multiple MHC class I HLA genes involved in regulating immune response via antigen presen-tation. The association between EBV gene expression and inhibition of MHC class I HLA expression implies that antigen display is either directly inhibited by EBV, facilitating immune evasion by tumor cells, and/or that tumor cells with inhibited presentation are selected for their ability to sustain higher levels of EBV to take maximum advantage of EBV oncogene-mediated tumor-promoting actions. Our data clearly reflect such tumor promotion, showing that deregulation of key proteins involved in apoptosis (BCL2-related protein Al and Fas apoptotic inhibitory molecule), cell cycle checkpoints (AKIP, SCYL1, and NDV), and metastasis (matrix metalloproteinase 1) is closely correlated with the levels of EBV gene expression in NPC.
AB - To identify the molecular mechanisms by which EBV-associated epithelial cancers are maintained, we measured the expression of essentially all human genes and all latent EBV genes in a collection of 31 laser-captured, microdissected nasopharyngeal carcinoma (NPC) tissue samples and 10 normal nasopharyngeal tissues. Global gene expression profiles clearly distinguished tumors from normal healthy epithelium. Expression levels of six viral genes (EBNA1, EBNA2, EBNA3A, EBNA3B, LMP1, and LMP2A) were correlated among themselves and strongly inversely correlated with the expression of a large subset of host genes. Among the human genes whose inhibition was most strongly correlated with increased EBV gene expression were multiple MHC class I HLA genes involved in regulating immune response via antigen presen-tation. The association between EBV gene expression and inhibition of MHC class I HLA expression implies that antigen display is either directly inhibited by EBV, facilitating immune evasion by tumor cells, and/or that tumor cells with inhibited presentation are selected for their ability to sustain higher levels of EBV to take maximum advantage of EBV oncogene-mediated tumor-promoting actions. Our data clearly reflect such tumor promotion, showing that deregulation of key proteins involved in apoptosis (BCL2-related protein Al and Fas apoptotic inhibitory molecule), cell cycle checkpoints (AKIP, SCYL1, and NDV), and metastasis (matrix metalloproteinase 1) is closely correlated with the levels of EBV gene expression in NPC.
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U2 - 10.1158/0008-5472.CAN-05-4399
DO - 10.1158/0008-5472.CAN-05-4399
M3 - Article
C2 - 16912175
AN - SCOPUS:33748031414
VL - 66
SP - 7999
EP - 8006
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 16
ER -