Bcl-xl and rag genes are induced and the response to il-2 enhanced in eμebna-1 transgenic mouse lymphocytes

Bcl-xl and rag genes are induced and the response to il-2 enhanced in eμebna-1 transgenic mouse lymphocytes


Play all audios:

Loading...

ABSTRACT We have described transgenic mice expressing Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) in B-cells which show a predisposition to lymphoma. To investigate the underlying


oncogenic mechanisms, we have cross bred transgenic strains of mice, examined the pre-tumour B-cell phenotype and investigated the expression levels of selected cellular genes as a response


to EBNA-1 expression. We have found that _bcl-x__L_ and the recombination activating genes (RAG) 1 and 2 are induced in pre-neoplastic samples of EBNA-1 expressing mice. Induction of


_bcl-x__L_ may explain the observed redundancy in lymphomagenesis between transgenic EBNA-1 and _bcl-2_. In addition, bone marrow cells derived from the EμEBNA-1 mice show a greater capacity


for cultured growth compared to controls, particularly in the presence of IL-2. Notably, _bcl-x__L_ expression is responsive to IL-2. These data shed new light on the potential contribution


of EBNA-1 to EBV associated tumorigenicity as well as to the viral life cycle and open a potential avenue for therapeutic intervention. Access through your institution Buy or subscribe This


is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00


per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated


during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS EPSTEIN BARR


VIRUS-MEDIATED TRANSFORMATION OF B CELLS FROM XIAP-DEFICIENT PATIENTS LEADS TO INCREASED EXPRESSION OF THE TUMOR SUPPRESSOR CADM1 Article Open access 22 October 2022 VIRAL TRANSDUCTION OF


PRIMARY HUMAN LYMPHOMA B CELLS REVEALS MECHANISMS OF NOTCH-MEDIATED IMMUNE ESCAPE Article Open access 20 October 2022 DELETION OF THE TRANSCRIPTIONAL REGULATOR TFAP4 ACCELERATES C-MYC-DRIVEN


LYMPHOMAGENESIS Article Open access 09 March 2023 REFERENCES * Adams JM, Cory S . 1992 _Cancer Surv._ 15: 119–141 * Berns A, Mikkers H, Krimpenfort P, Allen J, Scheijen B, Jonkers J . 1999


_Cancer Res._ 59: Suppl 1773–1777 * Bonnet M, Guinebretiere JM, Kremmer E, Grunewald V, Benhamou E, Contesso G, Joab I . 1999 _J. Natl. Cancer Inst._ 91: 1376–1381 * Gaffen SL . 2001


_Cytokine_ 14: 63–77 * Iscove NN, Sieber F, Winterhalter KH . 1974 _J. Cell. Physiol._ 83: 309–320 * Kang MS, Hung SC, Kieff E . 2001 _Proc. Natl. Acad. Sci. USA_ 98: 15233–15238 * Kapoor P,


Shire K, Frappier L . 2001 _EMBO J._ 20: 222–230 * Kawa K . 2000 _Int. J. Hematol._ 71: 108–117 * Kelsoe G . 1995 _Adv. Immunol._ 60: 267–288 * Kube D, Vockerodt M, Weber O, Hell K, Wolf J,


Haier B, Grasser FA, Muller-Lantzsch N, Kieff E, Diehl V, Tesch H . 1999 _J. Virol._ 73: 1630–1636 * Kuhn-Hallek I, Sage DR, Stein L, Groelle H, Fingeroth JD . 1995 _Blood_ 85: 1289–1299 *


Lee MA, Diamond ME, Yates JL . 1999 _J. Virol._ 73: 2974–2982 * McDonnell TJ, Deane N, Platt FM, Nunez G, Jaeger U, McKearn JP, Korsmeyer SJ . 1989 _Cell_ 57: 79–88 * McDonnell TJ, Korsmeyer


SJ . 1991 _Nature_ 349: 254–256 * Meru N, Jung A, Lisner R, Niedobitek G . 2001 _Int. J. Cancer_ 92: 75–78 * Motoyama N, Wang F, Roth KA, Sawa H, Nakayama K, Negishi I, Senju S, Zhang Q,


Fujii S _et al_ . 1995 _Science_ 267: 1506–1510 * Rickinson AB, Kieff E . 1996 _Fields Virology_ 3rd edn Fields BN, Knipe PM and Howley PM (eds) Philadelphia: Lippincott-Raven pp. 2360–2362


Google Scholar  * Srinivas SK, Sixbey JW . 1995 _J. Virol._ 69: 8155–8158 * Tsimbouri P, O'Donnell MA, Wilson JB . 2001 _Methods in Molecular Biology_ VOL 174: Wilson JB and May GHW


(eds) Totowa, NJ: The Humana Press Inc. pp. 411–421 Google Scholar  * Tuscano JM, Druey KM, Riva A, Pena J, Thompson CB, Kehrl JH . 1996 _Blood_ 88: 1359–1364 * Wilson JB . 1997 _EBV Report_


4: 63–72 * Wilson JB, Bell JL, Levine AJ . 1996 _EMBO J._ 15: 3117–3126 * Wilson JB, Drotar ME . 2001 _Methods in Molecular Biology_ VOL 174: Wilson JB and May GHW (eds) Totowa, NJ: The


Humana Press Inc. pp. 361–377 Google Scholar  * Wilson JB, Levine AJ . 1992 _Curr. Topics Microbiol. Immunol._ 182: 375–384 * Wu H, Ceccarelli DF, Frappier L . 2000 _EMBO Rep._ 1: 140–144


Download references ACKNOWLEDGEMENTS This work was supported by grants from the Leukaemia Research Fund and the Lady Tata Memorial Trust. The Bcl-2-Ig transgenic mouse line was a kind gift


from S Korsmeyer. Numerous individuals sent plasmid constructs for our use in generating probe fragments for which we are grateful. We thank Bill Cushley for assistance with the FACS


analyses and David Stevenson for critical reading of the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Molecular Genetics, Institute of Biomedical and Life Sciences,


University of Glasgow, Glasgow, G11 6NU, UK Penelope Tsimbouri, Mark E Drotar, Joanna L Coy & Joanna B Wilson Authors * Penelope Tsimbouri View author publications You can also search


for this author inPubMed Google Scholar * Mark E Drotar View author publications You can also search for this author inPubMed Google Scholar * Joanna L Coy View author publications You can


also search for this author inPubMed Google Scholar * Joanna B Wilson View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence


to Joanna B Wilson. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tsimbouri, P., Drotar, M., Coy, J. _et al._ _bcl-x__L_ and RAG genes are induced and


the response to IL-2 enhanced in EμEBNA-1 transgenic mouse lymphocytes. _Oncogene_ 21, 5182–5187 (2002). https://doi.org/10.1038/sj.onc.1205490 Download citation * Received: 17 September


2001 * Revised: 29 March 2002 * Accepted: 31 May 2002 * Published: 29 July 2002 * Issue Date: 01 August 2002 * DOI: https://doi.org/10.1038/sj.onc.1205490 SHARE THIS ARTICLE Anyone you share


the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer


Nature SharedIt content-sharing initiative KEYWORDS * EBV * EBNA-1 * IL-2 * Bcl-xL * transgenic mice * lymphoma