scholarly journals Epstein-Barr Virus Small RNAs Potentiate Tumorigenicity of Burkitt Lymphoma Cells Independently of an Effect on Apoptosis

2000 ◽  
Vol 74 (21) ◽  
pp. 10223-10228 ◽  
Author(s):  
Ingrid K. Ruf ◽  
Paul W. Rhyne ◽  
Chunying Yang ◽  
John L. Cleveland ◽  
Jeffery T. Sample
Keyword(s):  
Cell Survival ◽  
Cell Line ◽  
Burkitt Lymphoma ◽  
Small Rnas ◽  
Epstein Barr Virus ◽  
Wild Type ◽  
Barr Virus ◽  
Tumorigenic Potential ◽  
Epstein Barr ◽  
Dependent Mechanism

ABSTRACT The tumorigenic potential of the Burkitt lymphoma (BL) cell line Akata is dependent on the restricted latency program of Epstein-Barr virus (EBV) that is characteristically maintained in BL tumors. Within these cells, EBV-mediated inhibition of apoptosis correlates with an up-regulation of BCL-2 levels in concert with a down-regulation in c-MYC expression that occurs under growth-limiting conditions. Here we addressed whether EBV's effects on apoptosis and tumorigenicity are mediated by the EBV small RNAs EBER-1 and EBER-2. Stable expression of the EBERs in EBV-negative Akata BL cells, at levels comparable to those in EBV-positive cells, significantly enhanced the tumorigenic potential of EBV-negative BL cells in SCID mice, but did not fully restore tumorigenicity relative to EBV-positive Akata cells. Furthermore, wild-type or greater levels of EBER expression in EBV-negative Akata cells did not promote BL cell survival. These data therefore suggest that EBV can contribute to BL through at least two avenues: an EBER-dependent mechanism that enhances tumorigenic potential independent of a direct effect on apoptosis, and a second mechanism, mediated by an as-yet-unidentified EBV gene(s), that offsets the proapoptotic consequences of deregulated c-MYC in BL.

scholarly journals Oncogenic Role of Epstein-Barr Virus-Encoded RNAs in Burkitt’s Lymphoma Cell Line Akata

1999 ◽  
Vol 73 (12) ◽  
pp. 9827-9831 ◽  
Author(s):  
Jun Komano ◽  
Seiji Maruo ◽  
Koichi Kurozumi ◽  
Takanori Oda ◽  
Kenzo Takada
Keyword(s):  
Cell Line ◽  
Small Rnas ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Soft Agar ◽  
Burkitt's Lymphoma ◽  
Malignant Phenotype ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Our previous reports indicated that Epstein-Barr virus (EBV) contributes to the malignant phenotype and resistance to apoptosis in Burkitt’s lymphoma (BL) cell line Akata (N. Shimizu, A. Tanabe-Tochikura, Y. Kuroiwa, and K. Takada, J. Virol. 68:6069–6073, 1994; J. Komano, M. Sugiura, and K. Takada, J. Virol. 72:9150–9156, 1998). Here we report that the EBV-encoded small RNAs (EBERs) are responsible for these phenotypes. Transfection of the EBER genes into EBV-negative Akata clones restored the capacity for growth in soft agar, tumorigenicity in SCID mice, resistance to apoptotic inducers, and upregulated expression of bcl-2 oncoprotein that were originally retained in parental EBV-positive Akata cells and lost in EBV-negative subclones. This is the first report which provides evidence that virus-encoded RNAs (EBERs) have oncogenic functions in BL cells.

scholarly journals Epstein-Barr Virus-Encoded Bcl-2 Homologue Functions as a Survival Factor in Wp-Restricted Burkitt Lymphoma Cell Line P3HR-1

2009 ◽  
Vol 84 (6) ◽  
pp. 2893-2901 ◽  
Author(s):  
Ami Watanabe ◽  
Seiji Maruo ◽  
Taku Ito ◽  
Miho Ito ◽  
Koichi Ricardo Katsumura ◽  
...  
Keyword(s):  
Cell Line ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Virus Genome ◽  
Dominant Negative ◽  
Stable Transfection ◽  
Genome Maintenance ◽  
Barr Virus ◽  
Survival Factor ◽  
Epstein Barr

ABSTRACT Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus (EBV). EBV-positive BL tumors display two latent forms of infection. One is referred to as latency I infection, in which EBV expresses the virus genome maintenance protein EBNA1 as the only viral protein. The other is referred to as Wp-restricted latency and was recently identified in a subset of BL tumors. In these tumors, EBV expresses EBNA1, EBNA3A, EBNA3B, EBNA3C, a truncated form of EBNA-LP, and the viral Bcl-2 homologue BHRF1, all of which are driven by the BamHI W promoter (Wp). To investigate the role of EBV in Wp-restricted BL, we conditionally expressed a dominant-negative EBNA1 (dnEBNA1) mutant which interrupts the virus genome maintenance function of EBNA1 in the P3HR-1 BL cell line. Induction of dnEBNA1 expression caused loss of the EBV genome and resulted in apoptosis of P3HR-1 cells in the absence of exogenous apoptosis inducers, indicating that P3HR-1 cells cannot survive without EBV. Stable transfection of the BHRF1 gene into P3HR-1 cells rescued the cells from the apoptosis induced by dnEBNA1 expression, whereas stable transfection of truncated EBNA-LP, EBNA3A, or EBNA3C did not. Moreover, knockdown of BHRF1 expression in P3HR-1 cells resulted in increased cell death. These results indicate that EBV is essential for the survival of P3HR-1 cells and that BHRF1 functions as a survival factor. Our finding implies a critical contribution of BHRF1 to the pathogenesis of Wp-restricted BLs.

scholarly journals Integration of Epstein-Barr Virus into Chromosome 6q15 of Burkitt Lymphoma Cell Line (Raji) Induces Loss of BACH2 Expression

2004 ◽  
Vol 164 (3) ◽  
pp. 967-974 ◽  
Author(s):  
Tetsuya Takakuwa ◽  
Wen-Juan Luo ◽  
Maria Francisca Ham ◽  
Femiko Sakane-Ishikawa ◽  
Naoki Wada ◽  
...  
Keyword(s):  
Cell Line ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Barr Virus ◽  
Burkitt Lymphoma Cell ◽  
Burkitt Lymphoma Cell Line ◽  
Epstein Barr

Malignant transformation of B lymphoma cell line BJAB by Epstein-Barr virus-encoded small RNAs

FEBS Letters ◽  
2000 ◽  
Vol 484 (2) ◽  
pp. 153-158 ◽  
Author(s):  
Norio Yamamoto ◽  
Takenori Takizawa ◽  
Yoichi Iwanaga ◽  
Norio Shimizu ◽  
Naoki Yamamoto
Keyword(s):  
Cell Line ◽  
Malignant Transformation ◽  
Small Rnas ◽  
Epstein Barr Virus ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
B Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Epstein-Barr Virus Regulates c-MYC, Apoptosis, and Tumorigenicity in Burkitt Lymphoma

1999 ◽  
Vol 19 (3) ◽  
pp. 1651-1660 ◽  
Author(s):  
Ingrid K. Ruf ◽  
Paul W. Rhyne ◽  
Hui Yang ◽  
Corina M. Borza ◽  
Lindsey M. Hutt-Fletcher ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Type I ◽  
Oncogenic Potential ◽  
Barr Virus ◽  
B Cell Survival ◽  
Tumorigenic Potential ◽  
Steady State Levels ◽  
Epstein Barr ◽  
Novel Model

ABSTRACT Loss of the Epstein-Barr virus (EBV) genome from Akata Burkitt lymphoma (BL) cells is coincident with a loss of malignant phenotype, despite the fact that Akata and other EBV-positive BL cells express a restricted set of EBV gene products (type I latency) that are not known to overtly affect cell growth. Here we demonstrate that reestablishment of type I latency in EBV-negative Akata cells restores tumorigenicity and that tumorigenic potential correlates with an increased resistance to apoptosis under growth-limiting conditions. The antiapoptotic effect of EBV was associated with a higher level of Bcl-2 expression and an EBV-dependent decrease in steady-state levels of c-MYC protein. Although the EBV EBNA-1 protein is expressed in all EBV-associated tumors and is reported to have oncogenic potential, enforced expression of EBNA-1 alone in EBV-negative Akata cells failed to restore tumorigenicity or EBV-dependent down-regulation of c-MYC. These data provide direct evidence that EBV contributes to the tumorigenic potential of Burkitt lymphoma and suggest a novel model whereby a restricted latency program of EBV promotes B-cell survival, and thus virus persistence within an immune host, by selectively targeting the expression of c-MYC.

scholarly journals Epstein–Barr virus is integrated between REL and BCL-11A in American Burkitt lymphoma cell line (NAB-2)

2004 ◽  
Vol 84 (9) ◽  
pp. 1193-1199 ◽  
Author(s):  
Wen-Juan Luo ◽  
Tetsuya Takakuwa ◽  
Maria Francisca Ham ◽  
Naoki Wada ◽  
Angen Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Barr Virus ◽  
Burkitt Lymphoma Cell ◽  
Burkitt Lymphoma Cell Line ◽  
Epstein Barr
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