Bcl-2 reduces lymphomagenesis in deltaV-TCRbeta transgenic mice.
Overexpression of the bcl-2 oncogene in the lymphoid compartment of transgenic mice prolongs the lifespan of lymphocytes and leads to a low incidence of lymphomas at later age. Transgenic mice carrying a mutated T-cell receptor lacking the variable domain (deltaV-TCRbeta) suffer from lymphocyte depletion and are highly predisposed to lymphoma development. We intercrossed Bcl-2-Ig and deltaV-TCRbeta transgenic mice to assess whether Bcl-2 could synergize with deltaV-TCRbeta in tumorigenesis as reported previously for other oncogenes. Surprisingly, bitransgenic deltaV-TCRbeta; bcl-2-Ig mice showed a reduction in the incidence of lymphomas. Analyses of prelymphomatous mice showed that Bcl-2 restored some of the phenotypic aberrations caused by the deltaV-TCRbeta transgene in the lymphoid compartment. The inhibitory activity of Bcl-2 on deltaVTCRbeta-induced lymphomagenesis was not observed when both transgenes were crossed into the RAG-1-/- background suggesting an important role for more mature lymphocytes in this phenomenon. These results show that, depending on the specific conditions, overexpression of Bcl-2 can both promote as well as impair lymphoma development.
Acton
D
D
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
Jacobs
H
H
Domen
J
J
Berns
A
A
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003208:Concanavalin A / Q000494:pharmacology; D003433:Crosses, Genetic; D005260:Female; D015851:Interleukin-7 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008223:Lymphoma / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012737:Sex Factors; D013154:Spleen / Q000166:cytology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors
D015703:Antigens, CD; D015851:Interleukin-7; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003208:Concanavalin A; D016173:Macrophage Colony-Stimulating Factor