ORIGINAL PAPER Effect of Epstein–Barr virus infection on global gene expression in nasopharyngeal carcinoma (original) (raw)
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Effect of EpsteinBarr virus infection on global gene expression in nasopharyngeal carcinoma
Functional & integrative …, 2007
It was proposed that Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC); however, the molecular mechanisms involved in the effect of EBV on NPC host genes have not yet been well defined. For this study, two sets of microarray experiments, NPC (EBV-free) vs normal epithelial cells and EBV + vs EBV j NPC arrays, were analyzed and the datasets were crosscompared to identify any correlation between gene clusters involved in EBV targeting and the NPC host gene expression profiles. Statistical analysis revealed that EBV seems to have a preference for targeting more genes from the differentially expressed group in NPC cells than those from the ubiquitously expressed group. Furthermore, this trend is also reflected in log ratios where the EBV target genes of the differentially expressed group origin showed greater log ratios than genes with an origin from the ubiquitously expressed NPC group. Taken together, the genome-wide comparative scanning of EBV and NPC Funct Integr Genomics (2007) 7:79-93 transcriptomes has successfully demonstrated that EBV infection has an intensifying effect on the signals involved in NPC gene expression both in breadth (the majority of the genes) and in depth (greater log ratios).
Medicina
Nasopharyngeal carcinoma (NPC) is an uncommon type of malignancy/cancer worldwide. However, NPC is an endemic disease in southeast Asia and southern China and the reasons behind the underlying for such changes are unclear. Even though the Epstein–Barr infection (EBV) has been suggested as an important reason for undistinguishable NPC, the EBV itself is not adequate to source this type of cancer. The risk factors, for example, genetic susceptibility, and environmental factors might be associated with EBV to undertake a part in the NPC carcinogenesis. Normal healthy people have a memory B cell pool where the EBV persists, and any disturbance of this connection leads to virus-associated B cell malignancies. Less is known about the relationship between EBV and epithelial cell tumors, especially the EBV-associated nasopharyngeal carcinoma (EBVaNPC) and EBV-associated gastric carcinoma (EBVaGC). Currently, it is believed that premalignant genetic changes in epithelial cells contribute to ...
Epstein-Barr virus transcription in nasopharyngeal carcinoma
Journal of Virology, 1983
Sequences which encode Epstein-Barr virus (EBV) RNA in nasopharyngeal carcinoma (NPC) tissue have been identified. We utilized human biopsy material directly as well as NPC grown in nude mice. Total RNA was extracted from the tumor material and separated into polyadenylated and nonpolyadenylated fractions by oligodeoxythymidylate-cellulose chromatography. This material was used as template to construct 32P-labeled cDNA. The labeled cDNAs were hybridized to Southern blots of recombinant EBV DNA fragments. Three of the biopsies, F, 49, and 55, contained polyadenylated RNA homologous to the EBV BamHI fragments V and K, and EcoRI-DIJhet. These same fragments encode the most abundant polyribosomal RNAs in latently infected lymphoblastoid cell lines. The sequences which encoded nonpolyadenylated RNA in NPC tumor 49 were more extensive and included BamHI fragments C, V, B, E, and K, and EcoRI fragments DIJhet, E, F, and G1, a result that indicates selective polyadenylation in EBV RNA proce...
Epstein--Barr Virus Gene Expression in Nasopharyngeal Carcinoma
Journal of General Virology, 1988
Epstein-Barr virus (EBV), an agent with growth transforming potential for human B cells, is associated with certain B cell lymphomas in man and also with an epithelial tumour, undifferentiated nasopharyngeal carcinoma (NPC). Since B cell growth transformation is associated with the constitutive expression of a small number of EBV-coded latent proteins, the nuclear antigens EBNA 1, EBNA 2, EBNA 3 and EBNA-LP and the latent membrane protein (LMP), the present work sought to determine whether this same pattern of virus gene expression occurred in NPC. Tumour biopsies were taken from NPC patients from three areas of differing tumour incidence (Kenya, Algeria, Britain) and immediately snap-frozen, as were biopsies of non-EBV-related carcinomas for controls. Immunoblotting of PAGE-separated proteins with selected human sera identified 24 NPC biopsies clearly expressing EBNA 1. When the analysis was extended using selected human sera with antibodies against the other EBNAs, there was no detectable expression of EBNA 2, EBNA 3 or EBNA-LP in any of these 24 biopsies; their EBNA 2-negative status was confirmed using a monoclonal antibody (MAb) PE2 which was reactive in immunoblotting and in immunoprecipitation with EBNA 2A and EBNA 2B proteins. Similar experiments with two different LMP-specific MAbs, CS1 to 4 and S12, revealed heterogeneity between NPC biopsies; 9/24 biopsies were demonstrably LMP-positive, the degree of expression varying considerably between individual tumours in a manner which was not related to the level of EBNA 1 expression. None of the 24 NPC biopsies expressed detectable amounts of EBV lytic cycle antigens. A nude mouse-passaged NPC cell line, C15, likewise expressed EBNA 1 and LMP but none of the other EBV latent proteins nor lytic cycle antigens. This work identifies a novel type of EBV-cell interaction in NPC cells which is distinct from that seen in in vitro transformed B cell lines and from that seen to date in EBV-positive B cell lymphomas.
Epstein-Barr virus genes and nasopharyngeal cancer
2006
widespread in all areas of the world, infecting over 95% of the adult population. EBV primarily infects and replicates in the stratified squamous epithelium of the oropharynx during acute infection. Besides, its well-known tropism for B cells, the targets of EBV infection may also include epithelial cells, T cells, and cells of the macrocytic, granulocytic, and natural killer lineages. Although most humans coexist with the virus without serious sequelae, a small proportion will develop tumors. Almost every undifferentiated nasopharyngeal carcinoma (NPC) is EBV positive, despite geographical origin. EBV-derived IL-10 which is considered to play a role in the establishment of latent infection by suppression of the host immune system, may contribute to the growth of the tumor and to immune evasion. Latent membrane protein-1 (LMP-1) has transforming ability and support to the concept that EBV is involved in the pathogenesis of NPC. The association of NPC with EBV has been firmly established however the evidence indicating a role for the virus in the pathogenesis is still unknown and controversial. The main question is how the EBV-infected cells can escape from the immune response. [Turk J Cancer 2006;36(3):97-107].
Chinese journal of cancer, 2014
The interplay between host cell genetics and Epstein-Barr virus (EBV) infection contributes to the development of nasopharyngeal carcinoma (NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen (HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify t...
Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma
International Journal of Cancer, 1988
Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA I to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus D N A and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV D N A and expressed EBNA-I. O f 31 clinically diagnosed NPCs from China, 29 contained EBV D N A and 25 of these expressed EBNA-I. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-I. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the
Epstein-Barr virus DNA and epithelial markers in nasopharyngeal carcinoma
Medical Microbiology and Immunology, 2003
Nasopharyngeal carcinoma (NPC) belongs to the most common malignant tumours in certain parts of the world, e.g. South-East Asia. The undifferentiated type of NPC is associated with genomic Epstein-Barr virus (EBV) DNA. In normal epithelia of the nasopharynx cytokeratins (CK) 4, 5, 6, 13, 14, 15 and 19 are expressed. The aim of this study was to analyse the expression pattern of cytokeratins in NPC in the presence of EBV infection. Twenty primary or metastatic tumours from 13 patients suffering from a NPC were evaluated (formalin-fixed, paraffin-embedded). 35 S-labelled probes were used to detect EBV DNA in the tissue sections. Fourteen specimens (70%) were EBV positive. All positive specimens were undifferentiated NPC. All NPC were identified with broad-spectrum anti-CK antibody. Using a panel of anti-CK antibodies, there was no specific CK-expression pattern in NPC. In summary, undifferentiated NPC are strongly associated with EBV. The cytoskeleton of undifferentiated NPC reveals no specific pattern of CK expression.
Journal of General Virology, 1995
The presence of transcripts of the Epstein-Barr virus genes for Epstein-Barr nuclear antigen (EBNA)-I and EBNA-2 and for latent membrane protein (LMP)-I, LMP-2A and LMP-2B was investigated in 24 nasopharyngeal carcinoma (NPC) biopsies of Chinese origin and two NPC-derived solid tumour lines, CAO and C15, of Chinese and north African origin respectively, propagated by serial transplantation in nude mice. Transcripts were detected by PCR amplification of cDNA. EBNA-1 transcripts were present in all biopsies tested and originated exclusively from the FQ promoter while the C and W promoters were inactive. Using nested primers, LMP-1 and LMP-2B RNAs were found to be co-ordinately expressed in 22 of the 24 biopsies, while the two remaining tumours were negative for both. LMP-2A transcription was detected in 17 of the 22 LMP-l-positive biopsies. In summary, the following patterns of viral gene expression were observed in the tumour biopsies: (i) LMP-1-LMP-2B and LMP-2A positive (17 biopsies); (ii) LMP-1-LMP-2B positive but LMP-2A negative (five biopsies); (iii) no viral gene other than EBNA-1 expressed (two biopsies).
Epstein-Barr Virus Latent Membrane Protein-1 Expression in Nasopharyngeal Carcinoma
JCO Global Oncology
PURPOSE Nasopharyngeal carcinoma (NPC), a malignant neoplasm of the epithelium covering the nasopharynx, is a rare disease in most parts of the world. Epstein-Barr virus (EBV), the most potent oncogenic virus, coupled with environmental and genetic factors has been identified to play a role in the development of NPC. An array of methods for detecting the virus do exist, from serologic detection of antibodies to DNA amplification. There is paucity of local data on the status of EBV infection in relation to NPC within the region, and this study attempts to shed more light on the subject. METHODS This was a retrospective cross-sectional laboratory-based study on histologically confirmed, archived tissues from July 2015 to June 2019. Immunohistochemistry expression of latent membrane protein-1 (LMP-1) was used to detect EBV infection in the tissues. RESULTS A total of 71 cases were enrolled in this study. The mean age was 47.87 years ± 16.84 years with a male-to-female ratio of 1.5:1. T...