Cooperative interaction between Bcl-2 and Epstein-Barr virus latent membrane protein 1 in the growth transformation of human epithelial cells.

Lu, Ja-Yu; Chen, Jen‐Yang; Hsu, Tsuey-Ying; Yu, Winston C Y; Su, Ih‐Jen; Yang, Czau‐Siung

doi:10.1099/0022-1317-78-11-2975

Cited by 20 publications

(24 citation statements)

References 46 publications

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“…10,11 EBV has been shown to inhibit apoptosis by enhancing the expression of antiapoptotic genes, such as Bcl-2, which leads to immortalization of cells. 12 Despite the strong evidence implicating immunosuppression in the development of PTLD, this alone may be insufficient to fully explain why some patients develop PTLD. A second trigger may be required to activate the immune system, which is then deregulated because of the use of immunosuppressive therapy.…”

Section: Discussionmentioning

confidence: 99%

Increased Risk for Posttransplant Lymphoproliferative Disease in Recipients of Liver Transplants With Hepatitis C

McLaughlin

Wajstaub

Marotta

et al. 2000

Liver Transplantation

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Posttransplant lymphoproliferative disease (PTLD) is associated with immunosuppression and lymphotrophic viral infections. Hepatitis C virus (HCV) has been identified as a risk factor for non-Hodgkin's lymphoma, but no association between HCV and PTLD has been shown. To investigate this possibility, we identified patients with HCV who received their first orthotopic liver transplant at our unit between January 1, 1992, and December 31, 1996, and compared them with contemporary liver transplant recipients without HCV for incidence and risk factors for PTLD and survival. Fifty-seven patients with HCV and 127 patients without HCV were compared. There was no age difference (52 v 53 years; P ‫؍‬ .85), but there were more men in the HCV group (man-woman ratio, 2.1:1 v 0.9:1; P ‫؍‬ .006). No difference was observed in the follow-up period, graft survival, rejection episodes, or use of different immunosuppressive regimes (P > .05 for all). Four patients with HCV (7%) developed PTLD compared with 1 patient without HCV (0.8%; P ‫؍‬ .02). The relative odds for developing PTLD in patients with HCV were 9.5. All patients who developed PTLD were administered OKT3 induction therapy. These data suggest that PTLD may be more prevalent in patients undergoing liver transplantation for HCV-related liver disease who also receive OKT3, and that HCV infection may be a risk factor for developing PTLD. (Liver Transpl 2000;6: 570-574.)

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Section: Discussionmentioning

confidence: 99%

Increased Risk for Posttransplant Lymphoproliferative Disease in Recipients of Liver Transplants With Hepatitis C

McLaughlin

Wajstaub

Marotta

et al. 2000

Liver Transplantation

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“…The Bcl-2 and LMP-1 coexpressing cells (LB-2) were generated as described by us [24] . All cell cultures were maintained in 5% CO 2 at 37 ° in DMEM supplemented with 10% fetal calf serum (FCS), 100 U/ml of penicillin G and 100 g/ml of streptomycin sulphate.…”

Section: Methodsmentioning

confidence: 99%

“…Since the Bcl-2 and LMP-1 co-expressing cells could grow in anchorage-independent 0.33% semisoft agar with a colony-forming efficiency of 47% [24] , four groups of nude mice (5 each) were used for in vivo tumorigenicity analysis of Bcl-2/LMP-1 double-positive (LB-2), Bcl fig. 1 b).…”

Section: Cells Co-expressing Ebv Lmp-1 and Bcl-2 Can Form Tumors In Nmentioning

confidence: 99%

“…In epithelial cells, however, neither transient nor stable transfection with LMP-1 detectably affects Bcl-2 status [19,23] . We also investigated the effect of ectopic Bcl-2 expression on the growth and survival of the LMP-1-transfected epithelial cells, and showed that such co-expression of Bcl-2 and LMP-1 provided protection from LMP-1-induced apoptosis and altered the growth phenotype [24] .…”

Section: Introductionmentioning

confidence: 99%

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Tumor Formation in Nude Mice Inoculated with Cultured Human Epithelial Cells Co-Expressing Epstein-Barr Virus Latent Membrane Protein 1 and Bcl-2

Lay²

2007

Intervirology

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Aims: To examine the tumor-forming in nude mice of human epithelial cells co-expressed Bcl-2 and EBV LMP-1 ability, the phenotype of tumor cells and their expression of oncogenes and tumor-suppressor genes. Methods: Following an in vivo tumorigenesis test in nude mice, the phenotype and growth properties of tumor cells were observed. Levels of expression of Bcl-2, and EBV LMP-1, and of onco- and tumor-suppressor proteins were detected by Western blot assay. Results: Human epithelial cells co-expressing Bcl-2 and EBV LMP-1 can form tumors in nude mice. Tumors appeared 48–65 days postinoculation in 6 of 10 nude mice tested but not in mice given Bcl-2-positive (0/5), LMP-1-positive (0/5) and RHEK-1 control (0/5) cells. Levels of c-myc protein were upregulated by LMP-1 but were not affected by Bcl-2 in this cell background; screening for other cellular oncogene and tumor suppressor gene products showed no change. Conclusion: The complementary effects of EBV LMP-1 and Bcl-2 in human epithelial cells resulted in tumor formation in nude mice but did not affect the expression of onco- and tumor suppressor proteins except for elevated c-myc. These findings suggest that LMP-1 and Bcl-2 can contribute together to the formation of EBV-associated epithelial cell tumors.

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“…Studies have suggested that the immortalization effect of LMP-1 on B-lymphomas is mediated by the Bcl-2 gene in many lymphoid malignancies, and that the mediation may be through cooperation between Bcl-2 and MCL-1. Lu et al (1997) suggested that LMP-1-induced apoptosis is specifically blocked by the abnormal expression of Bcl-2 or co-expression of LMP-1 and Bcl-2 in epithelial cells (RHEK-1 cells). Down-regulation of Bcl-2 expression is also directly induced by LMP-1 when using antisense oligo-deoxynucleotides to suppress LMP-1 expression in an EBV-transformed B-cell line (Noguchi et al, 2001).…”

Section: Lmp-1 Specifically Up-regulates Bcl-2 Expressionmentioning

confidence: 99%

Epstein-Barr virus interactions with the Bcl-2 protein family and apoptosis in human tumor cells

Mao

2013

J. Zhejiang Univ. Sci. B

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Epstein-Barr virus (EBV), a human gammaherpesvirus carried by more than 90% of the world's population, is associated with malignant tumors such as Burkitt's lymphoma (BL), Hodgkin lymphoma, post-transplant lymphoma, extra-nodal natural killer/T cell lymphoma, and nasopharyngeal and gastric carcinomas in immune-compromised patients. In the process of infection, EBV faces challenges: the host cell environment is harsh, and the survival and apoptosis of host cells are precisely regulated. Only when host cells receive sufficient survival signals may they immortalize. To establish efficiently a lytic or long-term latent infection, EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways. This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors, which decide the fate of the host cell. The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma (Bcl) family are unknown. Still, EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host. We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.

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Cooperative interaction between Bcl-2 and Epstein-Barr virus latent membrane protein 1 in the growth transformation of human epithelial cells.

Cited by 20 publications

References 46 publications

Increased Risk for Posttransplant Lymphoproliferative Disease in Recipients of Liver Transplants With Hepatitis C

Increased Risk for Posttransplant Lymphoproliferative Disease in Recipients of Liver Transplants With Hepatitis C

Tumor Formation in Nude Mice Inoculated with Cultured Human Epithelial Cells Co-Expressing Epstein-Barr Virus Latent Membrane Protein 1 and Bcl-2

Epstein-Barr virus interactions with the Bcl-2 protein family and apoptosis in human tumor cells

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