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EBV interferes with the sensitivity of Burkitt lymphoma Akata cells to etoposide
Author(s) -
Lima Raquel T.,
Seca Hugo,
Soares Paula,
Nascimento Maria São José,
Vasconcelos M. Helena
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22920
Subject(s) - epstein–barr virus , apoptosis , small interfering rna , cell culture , etoposide , downregulation and upregulation , cancer research , lymphoma , biology , unfolded protein response , virus , microbiology and biotechnology , virology , immunology , transfection , gene , biochemistry , genetics , chemotherapy
Burkitt lymphoma (BL) commonly exhibits Epstein–Barr virus (EBV) positivity associated with latent chronic infection. Models of acute EBV infection have been associated with cellular resistance to apoptosis. However, the effect of latent long‐term EBV infection on apoptosis induced by drugs is not well defined. To determine this, we have studied the response of the Akata EBV+ cell line (type I latency) to etoposide, before and after downregulating EBV gene expression. We observed that downregulating EBV nuclear antigen‐1 (EBNA‐1) expression with siRNAs reverted cellular sensitivity to etoposide. In accordance with this finding, Akata EBV+ cells showed increased sensitivity to etoposide, when compared to the Akata EBV− cells. We also observed that Akata EBV+ cells presented increased apoptosis levels and decreased Bcl‐xL mRNA and protein levels, when compared to the Akata EBV− cells. In addition, Akata EBV+ cells contained less endoplasmic reticulum (ER) than EBV− cells. Finally, downregulation of EBV with EBNA‐1 siRNAs caused an increase in the expression of Bcl‐xL indicating that EBV is responsible for the differences found between the Akata EBV+ and EBV− cell lines. J. Cell. Biochem. 112: 200–210, 2011. © 2010 Wiley‐Liss, Inc.