scholarly journals Dysregulation of HER2/HER3 Signaling Axis in Epstein-Barr Virus-Infected Breast Carcinoma Cells

2007 ◽  
Vol 81 (11) ◽  
pp. 5705-5713 ◽  
Author(s):  
Jiun-Han Lin ◽  
Ching-Hwa Tsai ◽  
Jan-Show Chu ◽  
Jeou-Yuan Chen ◽  
Kenzo Takada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epstein Barr Virus ◽  
Soft Agar ◽  
Signaling Cascades ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Tumorigenic Activity

ABSTRACT The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer has been of long-standing interest to the field. Breast epithelial cells can be infected by EBV through direct contact with EBV-bearing lymphoblastoid cells, and EBV infection has recently been shown to confer breast cancer cells an increased resistance to chemotherapeutic drugs. In this study, we established EBV-infected breast cancer MCF7 and BT474 cells and demonstrated that EBV infection promotes tumorigenic activity of breast cancer cells. Firstly, we showed that the EBV-infected MCF7-A and BT474-A cells exhibited increased anchorage-independent growth in soft agar. The increased colony formation capacity in soft agar was associated with increased expression and activation of HER2/HER3 signaling cascades, as evidenced by the findings that the treatment of HER2 antibody trastuzumab (Herceptin), phosphatidylinositol 3-kinase inhibitor, or MEK inhibitor completely abolished the tumorigenic capacity. In the EBV-infected breast cancer cells, the expression of EBV latency genes including EBNA1, EBER1, and BARF0 was detected. We next showed that BARF0 alone was sufficient to efficiently up-regulate HER2/HER3 expression and promoted tumorigenic activity in MCF7 and BT474 cells by the use of both overexpression and small interfering RNA knock-down. Collectively, we demonstrated that EBV-encoded BARF0 promotes the tumorigenic activity of breast cancer cells through activation of HER2/HER3 signaling cascades.

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

2006 ◽  
Vol 80 (2) ◽  
pp. 845-853 ◽  
Author(s):  
Hratch Arbach ◽  
Viktor Viglasky ◽  
Florence Lefeu ◽  
Jean-Marc Guinebretière ◽  
Vanessa Ramirez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Epstein Barr Virus ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT 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.

Epstein–Barr virus and risk of breast cancer: a systematic review and meta-analysis

2019 ◽  
Vol 15 (24) ◽  
pp. 2873-2885 ◽  
Author(s):  
Mohammad Farahmand ◽  
Seyed Hamidreza Monavari ◽  
Zabihollah Shoja ◽  
Hadi Ghaffari ◽  
Mehdi Tavakoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epstein Barr Virus ◽  
Potential Role ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Despite the numerous publications regarding the role of Epstein–Barr virus (EBV) in breast cancer development, the topic has still remained controversial. The aim of the meta-analysis was to estimate the overall prevalence of EBV in the breast cancer population, and to investigate the association between EBV and breast cancer risk. The overall prevalence of EBV was calculated 26.37% (95% CI: 22–31%) from the 44 included studies. Meta-analysis of 30 case–control studies showed that the pooled association between EBV and risk of breast cancer is odds ratio 4.74 (95% CI: 2.92–7.69; Z = 6.30; p < 0.0001). Our analyses indicate a strong statistical relationship between EBV infection and risk of breast cancer, suggesting a potential role of EBV infection in the development of breast cancer.

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

2003 ◽  
Vol 77 (24) ◽  
pp. 13267-13274 ◽  
Author(s):  
J. Huang ◽  
H. Chen ◽  
L. Hutt-Fletcher ◽  
R. F. Ambinder ◽  
S. D. Hayward
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Breast Carcinoma ◽  
Reverse Transcription ◽  
Copy Number ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Ebv Infection ◽  
Reverse Transcription Pcr ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) has an accepted association with the epithelial malignancy nasopharyngeal carcinoma and has also been reported in other more controversial carcinoma settings. Evaluation of EBV association with epithelial carcinomas such as breast cancer would benefit from a better understanding of the outcome of EBV infection of these cells. Cell-free preparations of a green fluorescent protein-expressing virus, BX1, were used to infect breast cancer cell lines, which were then examined for EBV gene expression and viral genome copy number. Reverse transcription-PCR analyses revealed that the cells supported a mixture of latency II and lytic EBV gene expression. Lytic Zta and BMRF1 protein expression was detected by immunohistochemistry, and DNA PCR analyses estimated an EBV copy number of 300 to 600 genomes per infected cell. Evidence for lytic EBV expression was also found in breast tissue, where reverse transcription-PCR analyses detected lytic Zta transcripts in 7 of 10 breast carcinoma tissues and 4 of 10 normal tissues from the same patients. Scattered cells immunoreactive for Zta protein were also detectable in breast carcinoma. Quantitative real-time PCR analysis of EBV-positive breast carcinoma tissues suggested that less than 0.1% of the cells contained viral genomes. We suggest that sporadic lytic EBV infection may contribute to PCR-based detection of EBV in traditionally nonvirally associated epithelial malignancies.

scholarly journals Radiation-induced Epstein–Barr virus reactivation in gastric cancer cells with latent EBV infection

Tumor Biology ◽  
2017 ◽  
Vol 39 (7) ◽  
pp. 101042831771771 ◽  
Author(s):  
Athira Nandakumar ◽  
Futoshi Uwatoko ◽  
Megumi Yamamoto ◽  
Kazuo Tomita ◽  
Hideyuki J Majima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Epstein Barr Virus ◽  
Virus Reactivation ◽  
Gastric Cancer Cells ◽  
Barr Virus ◽  
Ebv Infection ◽  
Radiation Induced ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

scholarly journals Epstein-Barr Virus Contributes to the Malignant Phenotype and to Apoptosis Resistance in Burkitt’s Lymphoma Cell Line Akata

1998 ◽  
Vol 72 (11) ◽  
pp. 9150-9156 ◽  
Author(s):  
Jun Komano ◽  
Makoto Sugiura ◽  
Kenzo Takada
Keyword(s):  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Soft Agar ◽  
Burkitt's Lymphoma ◽  
Nuclear Antigen ◽  
Apoptosis Resistance ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT In the present study, we established an in vitro system representing the Burkitt’s lymphoma (BL)-type Epstein-Barr virus (EBV) infection which is characterized by expression of EBV-determined nuclear antigen 1 (EBNA-1) and absence of EBNA-2 and latent membrane protein 1 (LMP1) expression. EBV-negative cell clones isolated from the EBV-positive BL line Akata were infected with an EBV recombinant carrying a selectable marker, and the following selection culture easily yielded EBV-infected clones. EBV-reinfected clones showed BL-type EBV expression and restored the capacity for growth on soft agar and tumorigenicity in SCID mice that were originally retained in parental EBV-positive Akata cells and lost in EBV-negative subclones. Moreover, it was found that EBV-positive cells were more resistant to apoptosis than were EBV-negative cells. EBV-infected cells expressed the bcl-2 protein, through which cells might become resistant to apoptosis, at a higher level than did uninfected cells. This is the first report that BL-type EBV infection confers apoptosis resistance even in the absence of expression of LMP1 and BHRF1, both of which are known to have an antiapoptotic function. Surprisingly, transfection of the EBNA-1 gene into EBV-negative Akata clones could not restore malignant phenotypes and apoptosis resistance, thus suggesting that EBNA-1 alone was not sufficient for conferring them. Our results suggest that the persistence of EBV in BL cells is required for the cells to be more malignant and apoptosis resistant, which underlines the oncogenic role of EBV in BL genesis.

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