Bcl-2 reduces lymphomagenesis in deltaV-TCRbeta transgenic mice

Oncogene
D ActonA Berns

Abstract

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.

Citations

May 26, 2004·Cancer Letters·Arindam BhattacharyyaTanya Das
Mar 9, 2005·Cancer Research·Jehad CharoSteven A Rosenberg
Dec 7, 2000·Cancer Investigation·N DoninJ Leibovici
May 11, 2006·BMC Cell Biology·Teija L T AhoPäivi J Koskinen
Jun 6, 2000·Biochimica Et Biophysica Acta·S KayJ Leibovici
Apr 22, 2011·Blood·Daniel CorcosLouise S Matheson

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