Abstract |
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.
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Authors | Raquel T Lima, Hugo Seca, Paula Soares, Maria São José Nascimento, M Helena Vasconcelos |
Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 112
Issue 1
Pg. 200-10
(Jan 2011)
ISSN: 1097-4644 [Electronic] United States |
PMID | 21069730
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Epstein-Barr Virus Nuclear Antigens
- RNA, Messenger
- RNA, Small Interfering
- Viral Matrix Proteins
- bcl-X Protein
- Etoposide
- EBV-encoded nuclear antigen 1
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Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
- Burkitt Lymphoma
(virology)
- Cell Line, Tumor
- Down-Regulation
- Epstein-Barr Virus Nuclear Antigens
(genetics, metabolism)
- Etoposide
(pharmacology)
- Herpesvirus 4, Human
(pathogenicity)
- Humans
- RNA, Messenger
(metabolism)
- RNA, Small Interfering
(metabolism)
- Viral Matrix Proteins
(genetics, metabolism)
- bcl-X Protein
(genetics, metabolism)
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