Clonal transformation of human leukocytes by Epstein-barr virus in soft agar

1976 ◽  
Vol 17 (2) ◽  
pp. 191-196 ◽  
Author(s):  
Naoki Yamamoto ◽  
Yorio Hinuma
Keyword(s):  
Epstein Barr Virus ◽  
Soft Agar ◽  
Human Leukocytes ◽  
Barr Virus ◽  
Epstein Barr

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 Expression of an exogenous interleukin 6 gene in human Epstein Barr virus B cells confers growth advantage and in vivo tumorigenicity.

1990 ◽  
Vol 172 (1) ◽  
pp. 61-68 ◽  
Author(s):  
G Scala ◽  
I Quinto ◽  
M R Ruocco ◽  
A Arcucci ◽  
M Mallardo ◽  
...  
Keyword(s):  
B Cell ◽  
Interleukin 6 ◽  
Epstein Barr Virus ◽  
Constitutive Expression ◽  
Soft Agar ◽  
Malignant Phenotype ◽  
Barr Virus ◽  
Combined Action ◽  
Epstein Barr

The biological role of interleukin 6 (IL-6) molecules in human B cell tumorigenesis was studied by using an episomal expression vector, pHEBoSV-IL6, to introduce stably the human IL-6 gene into human Epstein Barr virus (EBV)-transformed B lymphoblasts. The gene was present in the IL-6-transfected cells in a high copy number and was efficiently expressed, resulting in the secretion of consistent levels of IL-6 molecules. The constitutive expression of the IL-6 gene led to an altered pattern of growth and to a malignant phenotype, as shown by clonogenicity in to an altered pattern of growth and to a malignant phenotype, as shown by clonogenicity in soft agar cultures and tumorigenicity in nude mice. These data suggest that the combined action of EBV, which exerts an immortalizing function, and of the growth-promoting activity of IL-6 molecules, can give rise to fully transformed B cell tumors in immunodeficient subjects.

scholarly journals Epstein-Barr Virus LMP2A Transforms Epithelial Cells, Inhibits Cell Differentiation, and Activates Akt

2000 ◽  
Vol 74 (22) ◽  
pp. 10681-10689 ◽  
Author(s):  
Frank Scholle ◽  
Katharine M. Bendt ◽  
Nancy Raab-Traub
Keyword(s):  
Cell Growth ◽  
Epithelial Cells ◽  
Nude Mice ◽  
Epstein Barr Virus ◽  
Soft Agar ◽  
Epithelial Differentiation ◽  
Pi3 Kinase ◽  
Hacat Cells ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT The Epstein-Barr virus LMP2A protein was expressed in a human keratinocyte cell line, HaCaT, and effects on epithelial cell growth were detected in organotypic raft cultures and in vivo in nude mice. Raft cultures derived from LMP2A-expressing cells were hyperproliferative, and epithelial differentiation was inhibited. The LMP2A-expressing HaCaT cells were able to grow anchorage independently and formed colonies in soft agar. HaCaT cells expressing LMP2A were highly tumorigenic and formed aggressive tumors in nude mice. The LMP2A tumors were poorly differentiated and highly proliferative, in contrast to occasional tumors that arose from parental HaCaT cells and vector control cells, which grew slowly and remained highly differentiated. Animals injected with LMP2A-expressing cells developed frequent metastases, which predominantly involved lymphoid organs. Involucrin, a marker of epithelial differentiation, and E-cadherin, involved in the maintenance of intercellular contact, were downregulated in LMP2A tumors. Whereas activation of the mitogen-activated protein kinase pathway was not observed, phosphatidylinositol-3-kinase (PI3-kinase)-dependent activation of the serine-threonine kinase Akt was detected in LMP2A-expressing cells and LMP2A tumors. Inhibition of this pathway blocked growth in soft agar. These data indicate that LMP2A greatly affects cell growth and differentiation pathways in epithelial cells, in part through activation of the PI3-kinase–Akt pathway.

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.

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