Lytic Viral Replication as a Contributor to theDetection of Epstein-Barr Virus in BreastCancer

Huang, Jui Chien; Chen, H.; Hutt-Fletcher, Lindsey; Ambinder, Richard F.; Hayward, S. Diane

doi:10.1128/jvi.77.24.13267-13274.2003

Cited by 46 publications

(53 citation statements)

References 53 publications

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“…In two tumors, BK3 and BK40, BZLF1 expression was observed after different overexposure of the blot. The pattern of expression is similar to what was seen in NPC (7) and in breast tissues (15).…”

Section: Resultssupporting

confidence: 64%

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol)

Arbach

Víglaský

Lefeu

et al. 2006

J Virol

103

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The Epstein-Barr virus (EBV) has been detected in subsets of breast cancers. In order to elaborate on these observations, we quantified by real-time PCR (Q-PCR) the EBV genome in biopsy specimens of breast cancer tissue as well as in tumor cells isolated by microdissection. Our findings show that EBV genomes can be detected by Q-PCR in about half of tumor specimens, usually in low copy numbers. However, we also found that the viral load is highly variable from tumor to tumor. Moreover, EBV genomes are heterogeneously distributed in morphologically identical tumor cells, with some clusters of isolated tumor cells containing relatively high genome numbers while other tumor cells isolated from the same specimen may be negative for EBV DNA. Using reverse transcription-PCR, we detected EBV gene transcripts: EBNA-1 in almost all of the EBV-positive tumors and RNA of the EBV oncoprotein LMP-1 in a smaller subset of the tissues analyzed. Moreover, BARF-1 RNA was detected in half of the cases studied. Furthermore, we observed that in vitro EBV infection of breast carcinoma cells confers resistance to paclitaxel (taxol) and provokes overexpression of a multidrug resistance gene (MDR1). Consequently, even if a small number of breast cancer cells are EBV infected, the impact of EBV infection on the efficiency of anticancer treatment might be of importance.The Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, is associated with the development of different epithelial malignancies (28), including nasopharyngeal carcinoma (NPC). It has also been linked with subsets of other types of carcinomas, including gastric carcinoma and lymphoepithelioma-like carcinoma in salivary glands and thymus (32,44). Several laboratories have reported detection of EBV in a subset of breast tumors (3,10,19,23). However, negative results have also been reported (6,9,14,27). Nevertheless, in most of the studies, a low viral load was detected in breast cancer biopsy specimens but the infected cells were not clearly identified. In the study presented here, we used real-time PCR (Q-PCR) to quantify the copy numbers of the EBV genome in biopsy specimens as well as in microdissected tumor cells. The results show that breast cancer cells harbor the viral genome. However, through microdissection and isolation of pure tumor cells, we now find that even in EBV-positive tumor samples, many tumor cells do not contain EBV genomes and that the breast carcinomas are highly heterogeneous in terms of genome content and distribution. Moreover, using reverse transcription-PCR (RT-PCR), we detected EBNA-1 and BARF-1 transcripts in almost all of the EBV-positive tumors and LMP-1 RNA in 3 of the 15 cases studied. The findings raise the possibility that although EBV is unlikely to have an etiologic role in the genesis of breast cancer, the virus might contribute to tumor progression. Finally, the potential impact of EBV in breast cancer progression was evaluated by estimation of resistance to chemotherapeutic agents on in vitro-infected MDA-MB-231 cells. The resul...

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Section: Resultssupporting

confidence: 64%

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol)

Arbach

Víglaský

Lefeu

et al. 2006

J Virol

103

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“…However, we observed that our results were compatible with the literature ones; it is possible that some prior findings may have been exaggerated by the phenomenon of lytic viral replication as identified by Huang et al [25]. The identification of EBV in this current study, using PCR standard, in situ PCR and immunohistochemistry, is consistent with the findings of others authors.…”

Section: Epstein-barr Virus (Ebv) Is a Human Herpesvirus Type 4 (Hhv-supporting

confidence: 83%

Molecular Detection of Epstein Barr Virus in Women with Breast Cancer in the West Algeria

Bensaber¹,

Bicout²,

Medjamia³

et al. 2017

JCT

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Breast cancer represents the most common malignant tumor afflicting women. This pathological condition remains the leading cause of death which constitutes an affliction that deserves considerable attention. As a result, the potential implication of viruses in its pathogenesis remains worth a hypothesis. The potential role of Epstein-Barr virus (EBV) in its pathogenesis is still a subject of continued discussion and investigations. The aim of this study is to evaluate a possible association between EBVs in breast cancers in western Algeria, and to determine the clinicopathological characteristics in order to specify the clinicopathological profile of tumors associated with this virus. We have searched the presence of EBV in 60 human breast cancer samples thanks to different techniques such as: PCR, in situ hybridization of EBER sequences and immunohistochemistry for latent membrane protein 1 (LMP1). The results obtained from this study showed the presence of this virus in only 16 cases or 26.6%. While the remaining 44 samples with a percentage of 73.3% showed a negative value. This may be due to sensitivity in the different techniques used and also what prompts us to suggest resuming the study using much more sensitive techniques such as real-time PCR. Our study indicates the presence of EBV DNA in a significant proportion of breast cancer in western Algeria. Further studies are required to clarify the role of this virus in breast carcinogenesis.

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“…2016; 11(3):e34806. (11,18,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). Table 1 shows a summary of the EBV-DNA positive subjects according to nationality, types of sample, and kinds of control tissue in the 20 selected studies.…”

Section: Resultsmentioning

confidence: 99%

“…As a result, four articles could be additionally identified (36,39,41,43), which should have been included in the SR by Huo et al (17) who performed an electronic search for articles published up to September 2010. Furthermore, an additional nine case-control studies published (45-53) thereafter were additionally acquired.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

Bae

Kim

2016

Arch Clin Infect Dis

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Context: The association between 'Epstein-Barr' virus (EBV) and breast cancer risk still remains controversial. A Systemic Review (SR) published in 2012 reported that there might be a statistically significant association between EBV and risk of breast cancer. However, errors were found in the appraisal process of the concerned SR. Objectives:The aim of this report was to conduct an adaptive meta-analysis with additional extraction of relevant papers published up until September 2015.Data Sources: The lists of references, cited articles and related articles provided by PubMed were made using the articles selected in the previous SR.Study Selection: Among these articles, only case-control studies using Polymerase Chain Reaction (PCR) techniques to detect EBV DNA in tissues were selected. Data Extraction: The summary odds ratio (SOR) and the 95% confidence interval (CI) were calculated though meta-analysis.Results: A total of 20 case-control studies were selected, and the total numbers of subjects in the case and control groups were 1947 and 1010, respectively. The findings of this meta-analysis revealed that EBV infection might increase the risk of breast cancer (SOR = 3.84, 95% CI: 2.24-6.58; I-squared = 62.2%). Sub-group analyses by region, sample type, and control tissue showed that a statistical significance of the risk was still secured. Conclusions:The findings of the meta-epidemiological study support that EBV infection may increase the risk of breast cancer. Nested case-control studies are required in the future.

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Lytic Viral Replication as a Contributor to theDetection of Epstein-Barr Virus in BreastCancer

Cited by 46 publications

References 53 publications

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol)

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol)

Molecular Detection of Epstein Barr Virus in Women with Breast Cancer in the West Algeria

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

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