bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EmuEBNA-1 transgenic mouse lymphocytes.
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-xL and the recombination activating genes (RAG) 1 and 2 are induced in pre-neoplastic samples of EBNA-1 expressing mice. Induction of bcl-xL may explain the observed redundancy in lymphomagenesis between transgenic EBNA-1 and bcl-2. In addition, bone marrow cells derived from the EmuEBNA-1 mice show a greater capacity for cultured growth compared to controls, particularly in the presence of IL-2. Notably, bcl-xL 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.
Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, UK.
Penelope
P
Tsimbouri
Mark E
ME
Drotar
Joanna L
JL
Coy
Joanna B
JB
Wilson
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D018398:Homeodomain Proteins; D007376:Interleukin-2; D015851:Interleukin-7; D015513:Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D051020:bcl-X Protein; C064658:RAG-1 protein; C417029:EBV-encoded nuclear antigen 1