Strain‐dependency of Chromosomal Abnormalities in Lymphomas Developed in Eμ‐<i>myc</i> Transgenic Mice

Akagi, Kiwamu; Yamamura, Ken‐ichi

doi:10.1111/j.1349-7006.2001.tb01122.x

Cited by 2 publications

(1 citation statement)

References 34 publications

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“…Because inbred mouse strains differ in lymphoma predisposition (50)(51)(52), these FVB mouse data do not exclude the possibility that EBNA1 could cause lymphoma in C57BL͞6 mice (40,53). For example, E -enhanced c-Myc expression induces pre-B and B lymphomas in C57BL͞6 mice, mostly T cell lymphomas in C3H mice, and T and B cell lymphomas in C57BL͞6 ϫ C3H F 1 mice (41,42,54).…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice

Kang

Yasui

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The lymphoma-inducing potential of Ig heavy-chain enhancer-and promoter-regulated Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) was evaluated in three transgenic FVB mouse lineages. EBNA1 was expressed at a higher level in transgenic B220(؉) splenocytes than in EBV-infected lymphoblastoid cell lines. EBNA1 was also expressed in B220(؊) transgenic splenocytes and thymocytes. Before killing and assessments at 18 -26 months, EBNA1-transgenic mice did not differ from control mice in mortality. At 18 -26 months EBNA1-transgenic mice did not differ from littermate control in ultimate body weight, in spleen size or weight, in lymph node, kidney, liver, or spleen histology, in splenocyte fractions positive for cluster of differentiation (CD)3 , CD4, CD8, CD62L, B220, CD5, IgM, IgD, MHC class II, CD11b, or CD25, or in serum IgM, IgG, or total Ig levels. Lymphomas were not found in spleens or other organs of 18-to 26-month-old EBNA1-transgenic (n ‫؍‬ 86) or control (n ‫؍‬ 45) FVB mice. EBNA1-transgenic lineages had a higher pulmonary adenoma prevalence than did littermate controls (39% versus 7%). However, the adenoma prevalence was not higher in EBNA1-transgenic mice than has been described for FVB mice, and EBNA1 was not expressed in normal pulmonary epithelia or adenomas.cancer ͉ herpesvirus ͉ latent ͉ persistence I n initial lymphocyte infection, Epstein-Barr Virus (EBV) causes B lymphocyte proliferation through a latency III program of expression of six nuclear proteins (EBNAs), two different integral membrane proteins, two small RNAs, and Bam A-initiated transcripts (1, 2). Although, in vitro, latency III-infected lymphocytes are able to grow endlessly as lymphoblastoid cell lines (LCLs), EBV proteins expressed in latency III-infected cells, in vivo, engender T cell responses that limit infected cell survival. EBV mostly persists long term in nonproliferating, latency I-or II-infected B cells that express EBNA1 or EBNA1 and latent infection membrane proteins, respectively (2-4). Latency I or latency II are also characteristic of Burkitt's lymphoma, Hodgkin's disease, and nasopharyngeal carcinoma (2). EBNA1 is expressed in almost all latent EBV infections and associated malignant diseases.EBNA1 enables efficient EBV episome replication, transcription, and maintenance in latently infected dividing cells (5-21). EBNA1 amino acids 379-641 include a dimerization and DNAbinding domain, which binds cognate 30-bp inverted repeat DNA sequences. EBV origin of plasmid replication (oriP) consists of 20 tandem cognate 30-bp repeats and four others 1 kbp away in a dyad symmetry (22). OriP has intrinsic origin activity. EBNA1 enhances oriP-dependent episome replication, transcription, and maintenance (7,8). EBNA1 amino acids 1-378 are necessary for chromosome association, transcriptional enhancement, and episome persistence, although not for initial DNA replication (21,(23)(24)(25). Within amino acids 1-378 is an irregular glycine͞alanine repeat, which inhibits EBNA1 processing through the proteasome͞TAP pathway (26,27).Becau...

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Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice

Kang

Yasui

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Svi3: A provirus common integration site in c‐myc in SL/Kh pre‐B lymphomas

et al. 2003

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t has been shown that retroviral insertions in host DNA may cause hematopoietic malignancies by enhancing the expression of a proto-oncogene or by disrupting tumor suppressor genes at the integration sites.1) Recent progress in the technique of retrotransposon tagging has greatly facilitated the identification of cancer-related genes.2) SL/Kh, a pre-B lymphoma-prone inbred mouse strain, provides a unique model to investigate the host genetic and epigenetic factors determining susceptibility and types of disease. 3)Mice of this strain develop spontaneous pre-B lymphomas at >90% incidence by 6 months of age. 4) Several lines of evidence indicate that the endogenous murine leukemia virus (MuLV) plays an etiologic role in the genesis of SL/Kh lymphoma. 5-7)Somatically acquired proviruses are frequently observed in the genomic DNAs of lymphomas. 6) By applying inverse polymerase chain reaction (IPCR), we have identified a number of virus integration hot spots in SL/Kh lymphoma DNA; we have named them SL/Kh virus integration sites (Svi) and numbered them serially in the order of discovery. 7) Svi3 is one of them, in which 3 out of 60 SL/Kh lymphomas had clonal integration of a provirus of the ecotropic MuLV within the promoter region and the first exon of the c-myc. The c-myc encodes a transcription factor that is a cellular homologue of the viral transforming gene encoded by the avian myelocytomatosis virus MC29. 8)Leukemias and lymphomas induced by retroviruses frequently have integration in or near the c-myc gene, 9,10) suggesting that these tumors are clonal or semi-clonal outgrowths of cells that acquired a selective growth advantage in vivo as a consequence of c-myc insertions. In this report, we will describe the provirus integrations at Svi3 and their biological effects in SL/Kh mouse lymphomagenesis. Materials and MethodsMouse strain. SL/Kh is an inbred mouse strain maintained in

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Strain‐dependency of Chromosomal Abnormalities in Lymphomas Developed in Eμ‐myc Transgenic Mice

Cited by 2 publications

References 34 publications

Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice

Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice

Svi3: A provirus common integration site in c‐myc in SL/Kh pre‐B lymphomas

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